Ion mobility spectrometer and method of operating same

ABSTRACT

In a drift tube partitioned into a plurality of cascaded drift tube segments each followed by an ion elimination region, for any integer M greater than 1, a method of separating ions repeats the following multiple times to cause only ions entering the drift tube that have a predefined ion mobility or range to traverse the drift tube: for each integer N beginning with 1 and sequentially advancing to M, establishing for a time duration an Nth electric repulsive field in the Nth ion elimination region and in every following Mth ion elimination region and an Nth electric drift field in each remaining ion elimination region and in each drift tube segment while deactivating for the time duration all non-Nth electric drift fields and non-Nth electric repulsive fields in each of the ion elimination regions and drift tube segments.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation of U.S. patent applicationSer. No. 13/844,901, which is a continuation-in-part of U.S. patentapplication Ser. No. 12/952,109, now U.S. Pat. No. 8,513,591, which is acontinuation-in-part of U.S. patent application Ser. No. 12/357,198, nowU.S. Pat. No. 7,838,821, which claims the benefit of, and priority to,U.S. Provisional Patent Application Ser. No. 61/021,785, the disclosuresof which are all incorporated herein by reference in their entirety.

GOVERNMENT RIGHTS

This invention was made with government support under AG024547, RR018942and 1RC1GM090797 awarded by the National Institutes of Health. TheUnited States Government has certain rights in the invention.

FIELD OF THE INVENTION

The present invention relates generally to ion separation instruments,and more specifically to instruments that separate ions in time as afunction of ion mobility.

BACKGROUND

Ion mobility spectrometers are analytical instruments that are used toseparate ions in time as a function of ion mobility. It is desirable tobe able to control electric fields applied to such instruments in orderto investigate properties of charged particles.

SUMMARY

The present invention may comprise one or more of the features recitedin the attached claims, and/or one or more of the following features andcombinations thereof. An ion mobility spectrometer instrument maycomprise a drift tube partitioned into a plurality of cascaded drifttube segments and ion elimination regions, each of the plurality ofdrift tube segments defining an ion inlet at one end, an ion outlet atan opposite end and a first distance between the ion inlet and the ionoutlet, each of the plurality of ion elimination regions defining asecond distance between the ion outlet of a different one of theplurality of drift tube segments and the ion inlet of the next adjacentdrift tube segment of the plurality of cascaded drift tube segments, anion source coupled to one of the plurality of cascaded drift tubesegments, one of an ion detector and an ion inlet of at least anotherion mobility spectrometer instrument arranged to receive ions exitingthe drift tube, a number, M, of electric field activation sources eachoperatively connected to one or more of the plurality of drift tubesegments such that, when activated, each establishes a repulsiveelectric field in a different one of the first M ion elimination regionsand in every following Mth ion elimination region, and also establishesan electric drift field in all remaining ion elimination regions and inall of the plurality of cascaded drift tube segments, and a controlcircuit to sequentially activate a number of times each of the number,M, of electric field activation sources while deactivating the remainingnumber, M, of electric field activation sources, with at least one ofthe M electric field activation sources having a different activationtime duration than activation times of others of the M electric fieldactivation sources, to thereby cause only ions generated by the ionsource that have a predefined ion mobility or range of ion mobilities totraverse the drift tube.

The plurality of cascaded drift tube segments and ion eliminationregions may illustratively define a linear drift tube, wherein the ionsource is coupled to the ion inlet of a first one of the cascaded drifttube segments, and wherein the one of the ion detector and the ion inletof the at least another ion mobility spectrometer instrument is coupledby a last one of the plurality of ion elimination regions to the ionoutlet of a last one of the plurality of drift tube segments. In thisimplementation, the ions generated at the ion source travel from the ioninlet of the first one of the cascaded drift tube segments through thelast one of the plurality of ion elimination regions under the influenceof electric drift fields established by the M electric field activationsources in the plurality of cascaded drift tube segments and ionelimination regions, and ions having ion mobilities or ranges of ionmobilities other than the predefined ion mobility or range of ionmobilities are filtered out by the repulsive electric fields establishedby each of the M electric field activation sources in a different one ofthe first M ion elimination regions and in every following Mth ionelimination region. In one embodiment of this implementation, the ionsource may continuously generate ions, and the continuously generatedions may enter the first one of the cascaded drift tube segments underthe influence of the electric drift field sequentially established byeach of the plurality, M, of electric field activation sources in thefirst one of the cascaded drift tube segments. Alternatively, the ioninlet of the first one of the cascaded drift tube segments may comprisean ion gate, and the control circuit may control the ion gate toselectively allow entrance of discrete packets of ions generated by theion source into the ion inlet of the first one of the cascaded drifttube segments.

In an alternative embodiment, the ion outlet of a last one of the drifttube segments is coupled by a last ion elimination region to the ioninlet of a first one of the drift tube segments such that the drift tubedefines therein a closed and continuous ion travel path, and the ionmobility spectrometer may further comprise an ion entrance drift tubesegment having an ion inlet coupled to the ion source and an ion outletcoupled to the one of the plurality of cascaded drift tube segments, anion exit drift tube segment having an ion inlet coupled to the one oranother one of the plurality of drift tube segments, and an ion outlet,and an ion gate arrangement responsive to a first set of one or more iongate signals to direct ions moving through the drift tube through theone or another one of the plurality of cascaded drift tube segmentswhile blocking the ions from entering the ion exit drift tube segment,and to a second set of one or more ion gate signals to direct the ionsmoving through the drift tube into the ion exit drift tube segment whileblocking the ions from moving through the one or another one of theplurality of cascaded drift tube segments, wherein the control circuitmay produce the first set of one or more ion gate signals to cause onlyions supplied by the ion source that have the predefined ion mobility orrange of ion mobilities to travel through the drift tube, and after theions have traveled around the drift tube a selected number of times toproduce the second set of one or more ion gate signals to draw ionsmoving through the drift tube out of the drift tube and into the ionexit drift tube segment where the ions exit via the ion mobilityspectrometer via the ion outlet of the ion exit drift tube segment. Theion gate arrangement may comprise a first ion gate positioned in the oneor another one of the plurality of cascaded drift tube segments, and asecond ion gate positioned in or at the ion inlet of the ion exit drifttube segment, wherein the first set of one or more ion gate signalscomprises a first ion gate signal to which the first ion gate isresponsive to allow ions to pass therethrough and a second ion gatesignal to which the second ion gate is responsive to block ions frompassing therethrough, and wherein the second set of one or more ion gatesignals comprises a third ion gate signal to which the first ion gate isresponsive to block ions from passing therethrough and a fourth ion gatesignal to which the second ion gate is responsive to allow ions to passtherethrough. In this implementation, ions generated at the ion sourcetravel from the ion inlet of the first one of the cascaded drift tubesegments through the last one of the plurality of ion eliminationregions under the influence of electric drift fields established by thenumber, M, of electric field activation sources in the plurality ofcascaded drift tube segments and ion elimination regions, and ionshaving ion mobilities or ranges of ion mobilities other than thepredefined ion mobility or range of ion mobilities are filtered out bythe repulsive electric fields established by each of the number, M, ofelectric field activation sources in a different one of the first M ionelimination regions and in every following Mth ion elimination region.In one embodiment of this implementation, the ion source maycontinuously generates ions, and at least one of the number, M, ofelectric field activation sources may establish an electric drift fieldin the ion entrance drift tube, and the continuously generated ions mayenter the ion inlet of the ion entrance drift tube segment under theinfluence of the electric drift field established in the ion entrancedrift tube. In an alternate embodiment of this implementation, the ioninlet of the ion entrance drift tube segment may comprise an ion gate,and the control circuit may control the ion gate to selectively allowentrance of discrete packets of ions generated by the ion source intothe ion inlet of the ion entrance drift tube segment.

In either implementation, the ion source may comprise at least one ionseparation instrument configured to separate ions in time as a functionof one or more molecular characteristics.

In either implementation, each of the number, M, of electric fieldactivation sources may be programmable, in one embodiment, to establish,when triggered, the electric drift and repulsive fields, and the controlcircuit may be configured to sequentially activate the number, M, ofelectric field activation sources for by sequentially triggering thenumber, M, of electric field activation sources. Alternatively, each ofthe number, M, of electric field activation sources may be programmableto establish, when triggered, the electric drift and repulsive fields,and the control circuit may be configured to sequentially activate thenumber, M, of electric field activation sources by triggering one of thenumber, M, of electric field activations sources with remaining ones ofthe number, M, of electric field activation sources being triggered byoperation of a previously triggered one of the number, M, of electricfield activation sources.

In either implementation, fundamental frequency is defined by a ratio ofa total number of the plurality of drift tube segments and a total drifttime of ions having the predefined ion mobility or range of ionmobilities through the drift tube under the influence of the electricfields established by the number, M, of electric field activationsources, and the control circuit may sequentially activate each of thenumber, M, of electric field activation sources while deactivating theremaining number, M, of electric field activation sources a number oftimes at a plurality of different activation durations to therebyproduce ions exiting the drift tube at a number of different overtonefrequencies that are functionally related to the fundamental frequency.The ion mobility spectrometer instrument may further comprise the iondetector coupled by a last one of the plurality of ion eliminationregions to the ion outlet of a last one of the plurality of drift tubesegments, and the ion detector may produce ion detection signals inresponse to detection of ions thereat, and the control circuit mayconvert the ion detection signals to the frequency domain foridentification of ion intensity signals at the number of differentovertone frequencies.

An ion mobility spectrometer instrument may comprise a drift tubepartitioned into a plurality of cascaded drift tube segments and ionelimination regions, each of the plurality of drift tube segmentsdefining an ion inlet at one end, an ion outlet at an opposite end and afirst distance between the ion inlet and the ion outlet, each of theplurality of ion elimination regions defining a second distance betweenthe ion outlet of a different one of the plurality of drift tubesegments and the ion inlet of the next adjacent drift tube segment ofthe plurality of cascaded drift tube segments, an ion source coupled toone of the plurality of cascaded drift tube segments, one of an iondetector and an ion inlet of at least another ion mobility spectrometerinstrument arranged to receive ions exiting the drift tube, an integernumber, φ, of electric field activation sources each operativelyconnected to one or more of the plurality of drift tube segments suchthat, when activated, each establishes a repulsive electric field in adifferent one of the first φ ion elimination regions and in everyfollowing φth ion elimination region, and also establishes an electricdrift field in all remaining ion elimination regions and in all of theplurality of cascaded drift tube segments, and a control circuit tosequentially activate a number of times each of the integer number, φ,of electric field activation sources for an activation duration whiledeactivating the remaining integer number, φ, of electric fieldactivation sources to thereby cause only ions generated by the ionsource that have a predefined ion mobility or range of ion mobilities totraverse the drift tube, a ratio of the activation duration of one ofthe M electric field activation sources and the activation duration ofat least one of the remaining electric field activation sources defininga phase ratio, ζ, the control circuit to control the activationdurations of each of the integer number, φ, of electric field activationsources such that ζ>0 and ζ≠1.

A fundamental frequency, f_(f), is defined by a ratio of a total numberof the plurality of drift tube segments and a total drift time of ionshaving the predefined ion mobility or range of ion mobilities throughthe drift tube under the influence of the electric fields established bythe integer number, φ, of electric field activation sources, and thecontrol circuit may sequentially activate each of the integer number, φ,of electric field activation sources while deactivating the remaininginteger number, φ, of electric field activation sources a number oftimes at a plurality of different activation durations to therebyproduce ions exiting the drift tube at a number of different overtonefrequencies, f_(h), that are functionally related to the fundamentalfrequency, f_(f), by the relationship f_(h)=f_(f)[φh+1][(φ−1)ζ+1]/φ,where h defines an integer index beginning with zero and having a stepsize of 1. Alternatively or additionally, the control circuit maysequentially activate each of the integer number, φ, of electric fieldactivation sources while deactivating the remaining integer number, φ,of electric field activation sources a number of times with a sum of theactivation durations of each of the integer number, φ, of electric fieldactivation sources defined as a ratio of φ and the fundamentalfrequency, f_(f), to thereby produce ions exiting the drift tube at anovertone, m, of the fundamental frequency defined by the relationshipm=(ζ+1)/2.

In a specific implementation of the ion spectrometer instrument, φ=2such that a first one of the two electric field activation sources, whenactivated, establishes a repulsive electric field in sequentially oddnumbered ones of the plurality of ion elimination regions and anelectric drift field in sequentially even numbered ones of the pluralityof ion elimination regions and also in each of the plurality of cascadeddrift tube segments, and a second one of the two electric fieldactivation sources, when activated, establishes a repulsive electricfield in sequentially even numbered ones of the plurality of ionelimination regions and an electric drift field in sequentially oddnumbered ones of the plurality of ion elimination regions and also ineach of the plurality of cascaded drift tube segments, and wherein thephase ratio, ζ, is the ratio of the activation duration of the first oneof the electric field activation sources and the activation duration ofthe second one of the electric field activation sources. In thisimplementation, a fundamental frequency, f_(f), is defined by a ratio ofa total number of the plurality of drift tube segments and a total drifttime of ions having the predefined ion mobility or range of ionmobilities through the drift tube under the influence of the electricfields established by the two electric field activation sources, and thecontrol circuit to sequentially activate one of the two electric fieldactivation sources while deactivating the other of the two electricfield activation sources a number of times at a plurality of differentactivation durations to thereby produce ions exiting the drift tube at anumber of different overtone frequencies, f_(h), that are functionallyrelated to the fundamental frequency, f_(f), by the relationshipf_(h)=f_(f[)2h+1][ζ+1]/2, where h defines an integer index beginningwith zero and having a step size of 1. Alternatively or additionally,the control circuit may sequentially activate one of the two electricfield activation sources while deactivating the other of the twoelectric field activation sources a number of times with a sum of theactivation duration of the first one of the electric field activationsources and the activation duration of the second one of the electricfield activation sources defined as a ratio of 2 and the fundamentalfrequency, f_(f), to thereby produce ions exiting the drift tube at anovertone, m, of the fundamental frequency defined by the relationshipm=(ζ+1)/2.

A method is provided for separating ions as a function of ion mobilityin a drift tube partitioned into a plurality of cascaded drift tubesegments each defining an ion inlet at one end and an ion outlet at anopposite end, wherein the plurality of cascaded drift tube segmentsdefine an ion elimination region between an ion outlet of each drifttube segment and an ion inlet of an adjacent drift tube segment. Themethod may comprise deactivating a second electric repulsive field and asecond electric drift field and establishing a first electric repulsivefield in odd-numbered ones of the ion elimination regions while alsoestablishing a first electric drift field in even-numbered ones of theion elimination regions and in each of the drift tube segments for afirst time duration, deactivating the first electric repulsive field andthe first electric drift field and establishing the second electricrepulsive field in even-numbered ones of the ion elimination regionswhile also establishing a second electric drift field in odd-numberedones of the ion elimination regions and in each of the drift tubesegments for a second time duration different than the first timeduration, and sequentially repeating the two deactivating steps a numberof times to thereby cause only ions entering the ion inlet of a firstone of the plurality of cascaded drift tube regions that have apredefined ion mobility or range of ion mobilities to traverse the drifttube.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of one illustrative embodiment of an ionmobility spectrometer instrument.

FIG. 2 is a diagram of one illustrative embodiment of the drift tube andassociated arrangement of the electric field activation sources of theion mobility spectrometer of FIG. 1.

FIG. 3 is a timing diagram illustrating operation of the ion mobilityspectrometer of FIGS. 1 and 2.

FIG. 4A is a diagram of one several cascaded sections of the drift tubeillustrated in FIG. 2.

FIGS. 4B-4D illustrate alternate embodiments of the arrangement of theelectric field activation sources relative to the drift tube of FIG. 4A.

FIG. 5 is a flowchart of one illustrative process for operating the ionmobility spectrometer of either of FIG. 1 or 3 as an ion mobility filteroperable to produce only ions having a selected mobility or range ofmobilities from a continuous or discrete ion source.

FIG. 6 is a plot of ion intensity vs. drift time illustrating the drifttime of ions of the sodiated monomer [M+Na]⁺ form of the simpleoligosaccharide isomer raffinose through one particular embodiment ofthe ion mobility spectrometer of FIG. 1.

FIG. 7 is a flowchart of one illustrative process for operating the ionmobility spectrometer of either of FIG. 1 or 3 by sweeping the pulsewidths of the electric field activation sources over a range of pulsewidth durations.

FIG. 8 is a plot of ion intensity vs. frequency illustrating the resultin the frequency domain of the process of FIG. 7 using a continuoussource of raffinose ions.

FIG. 9 includes a number of plots of ion intensity vs. frequencyillustrating results in the frequency domain of the process of FIG. 7applied to ion mobility instruments having different phase numbers.

FIG. 10 includes a number of plots of ion intensity vs. frequencyillustrating results in the frequency domain of the process of FIG. 5applied to ion mobility instruments having different numbers of drifttube sections.

FIG. 11 includes a number of plots of ion intensity vs. frequencyillustrating results in the frequency domain of the process of FIG. 7applied to a raffinose sample, a melezitose sample and to a samplemixture of raffinose and melezitose.

FIG. 12A includes a number of plots of ion intensity vs. total drifttime illustrating results in the time domain of the process of FIG. 5applied to a raffinose/melezitose mixture using a cyclotron geometry ionmobility spectrometer.

FIG. 12B is a diagram of one illustrative embodiment of a cyclotrongeometry ion mobility spectrometer used to generate the plots of FIG.12A.

FIG. 13 is a block diagram of one illustrative embodiment of a cascadedion mobility spectrometer instrument that employs some of the conceptsillustrated and described with respect to FIGS. 1-12B.

FIG. 14 is a flowchart of one illustrative process for operating the ionmobility spectrometer of FIG. 12B by first pre-filling the drift tubewith ions and then sequentially controlling the electric fieldactivation sources to direct ions some number of revolutions around thedrift tube in a manner that resolves only ions having a selectedmobility or range of mobilities.

FIG. 15 is a flowchart of another illustrative process for operating theion mobility spectrometer of FIG. 12B by sequentially controlling theelectric field activation sources to direct ions having a selectedmobility or range of mobilities around the drift tube while alsoperiodically introducing new ions into the drift tube from the ionsource, and then continuing to sequentially control the electric fieldactivation sources to direct ions having the selected mobility or rangeof mobilities some number of revolutions around the drift tube withoutintroducing new ions into the drift tube such that only ions within thedrift tube having the selected mobility or range of mobilities areresolved.

FIGS. 16A-16L are successive or sequential block diagrams of oneillustrative embodiment of the ion mobility spectrometer of FIG. 12Billustrating operation of the spectrometer during the part of theprocess illustrated in the flowchart of FIG. 15 in which the electricfield activation sources are sequentially controlled to direct ionshaving a selected mobility or range of mobilities around the drift tubewhile also periodically introducing new ions into the drift tube fromthe ion source.

FIG. 17 is a block diagram of another illustrative embodiment of an ionmobility spectrometer instrument.

FIG. 18 is a block diagram of the ion mobility spectrometer of FIG. 1illustrating one illustrative technique controlling electric fieldswithin some of the drift tube segments adjacent to the ion entrance andion exit ends when operating a linear drift tube ion mobilityspectrometer to direct ions back and forth between the two ends of thedrift tube in a manner that resolves only ions having a selectedmobility or range of mobilities.

FIG. 19 is a block diagram of yet another illustrative embodiment of anion mobility spectrometer instrument.

FIG. 20 is a flowchart of one illustrative process for operating the ionmobility spectrometer of FIG. 19 by sequentially controlling theelectric field activation sources to direct ions back and forth betweenthe ends of the drift tube in a manner that resolves only ions having aselected mobility or range of mobilities.

FIG. 21 is a block diagram of still another illustrative embodiment ofan ion mobility spectrometer.

FIG. 22A is a timing diagram illustrating a series of drift tubesegments operated with a two-phase arrangement of electric fieldactivation sources having equal activation durations selected to definethe 3^(rd) overtone of the fundamental frequency of operation.

FIG. 22B is a timing diagram similar to FIG. 22A and illustrating thetwo-phase arrangement of electric field activation sources havingunequal activation durations also selected to define the 3^(rd) overtoneof the fundamental frequency of operation.

FIG. 23A is a plot of ion intensity vs. frequency illustrating theresult in the frequency domain of a simulated spectra in which a phaseratio of activation durations of two electric field activation sourcesin a two-phase application is set to unity.

FIG. 23B is a plot of ion intensity vs. frequency illustrating theresult in the frequency domain of a simulated spectra in which a phaseratio of activation durations of two electric field activation sourcesin a two-phase application is set to 5.

FIG. 24 is a flowchart of a process for operating a two-phase ionmobility spectrometer of the type illustrated and described herein byselecting a phase ratio of the activation durations of the two electricfield activation sources to transmit ions through the drift tube at acorresponding selected overtone frequency.

FIG. 25 is a flowchart of a process for operating a two-phase ionmobility spectrometer of the type illustrated and described herein byselecting a phase ratio of the activation durations of the two electricfield activation sources and sweeping the two activation durations overa range of frequencies to transmit ions through the drift tube at acorresponding set of overtone frequencies.

FIG. 26A is a plot of ion intensity vs. frequency illustrating theresult in the frequency domain of a simulated spectra in which a phaseratio of activation durations of two electric field activation sourcesin a two-phase application is set to 3 and the activation durations ofthe two electric field activation sources are swept over a range offrequencies according to the process illustrated in FIG. 25.

FIG. 26B is a plot of ion intensity vs. frequency illustrating theresult in the frequency domain of a simulated spectra in which a phaseratio of activation durations of two electric field activation sourcesin a two-phase application is set to a non-integer number and theactivation durations of the two electric field activation sources areswept over a range of frequencies according to the process illustratedin FIG. 25.

FIG. 27 is a flowchart of a process for operating a two-phase ionmobility spectrometer of the type illustrated and described herein byselecting an operating frequency of interest and changing phase ratiosof the activation durations of the two electric field activation sourcesover a range of phase ratios to investigate overtones at the selectedfrequency for the selected set of phase ratios.

FIG. 28 is a flowchart of a process for operating a two-phase ionmobility spectrometer of the type illustrated and described herein byselecting sweeping the electric field activation source operatingfrequency over a range of frequencies for each of number of differentphase ratios of the activation durations of the two electric fieldactivation sources to investigate overtones in a range of frequenciesfor the selected set of phase ratios.

DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS

For the purposes of promoting an understanding of the principles of theinvention, reference will now be made to a number of illustrativeembodiments shown in the attached drawings and specific language will beused to describe the same.

Referring to FIG. 1, a block diagram is shown of one illustrativeembodiment of an ion mobility spectrometer instrument 10. In theillustrated embodiment, the ion mobility spectrometer instrument 10includes an ion source 12 having an ion outlet that is couple to an ioninlet of a drift tube 14. An ion outlet of the drift tube 14 is coupledto an ion detector 16 having a signal output that is electricallyconnected to an input of a control circuit 18. The control circuit 18includes a conventional memory unit 20, and further includes aconventional clock circuit 22 that may be controlled by the controlcircuit 18 in a conventional manner to produce periodic signals ofdesired frequency. Illustratively, a source of buffer gas 24 suppliesbuffer gas to the drift tube 14 in a conventional manner.

The control circuit 18 is electrically connected to a control input ofan ion source voltage supply, V_(IS), having a number, K, of outputsthat are electrically connected to the ion source 12, where K may be anypositive integer. The ion source 12 may be any conventional ion sourcethat is configured to controllably produce ions from one or moresamples. The ion source voltage supply, V_(IS), may accordinglyrepresent one or more voltage supplies configured to controllablyproduce, under the control of the control circuit 18 and/or manuallycontrollable or programmable, one or more corresponding voltages forcontrolling operation of the ion source 12 in a conventional manner toproduce ions. Illustratively, the ion source 12 may be configured tocontinuously produce ions, or may alternatively be configured to producediscrete packets of ions. Examples of such conventional ion sourcesinclude, but are not limited to, electrospray ion sources (ESI), ionsources using radiation source to desorb ions from a sample, e.g.,matrix-assisted laser desorption ion sources (MALDI), ion sources thatcollect generated ions in an ion trap for subsequent release, and thelike. Alternatively or additionally, the ion source 12 may be or includeone or more conventional ion separation instruments configured toseparate ions in time as a function of one or more molecularcharacteristics. Examples include, but are not limited to, aconventional liquid or gas chromatograph, a conventional massspectrometer, a conventional ion mobility spectrometer, a capillaryelectrophoresis instrument, or the like. In any case, ions produced bythe ion source 12 exit an ion outlet of the ion source 12 and enter anion inlet of the drift tube 14 of the ion mobility spectrometerinstrument 10.

The ion mobility spectrometer 10 further includes a number, M, ofelectric field activation sources, e.g., voltage sources, V₁-V_(M),where M may be any positive integer greater than 1. In the illustratedembodiment, the control circuit 18 includes a corresponding number ofoutputs, each of which is electrically connected to an input of adifferent one of the electric field activation sources, V₁-V_(M). Inalternate embodiments, the control circuit 18 may include fewer outputsthat are electrically connected to corresponding inputs of fewer of theelectric field activation sources, V₁-V_(M). In such embodiments, someof which will be described in detail hereinafter, one or more of theelectric field activation sources, V₁-V_(M), may be electricallyconnected to corresponding outputs of the control circuit 18 and one ormore others of the electric field activation sources, V₁-V_(M), may betriggered by operation of an adjacent or other ones of the electricfield activation sources, V₁-V_(M), and/or be programmed for specifiedoperation. In any case, the outputs of the voltage sources V₁-V_(M) areelectrically connected to the drift tube 14 in a manner that will befully described in detail hereinafter.

In the illustrated embodiment, the ion detector 16 is conventional andis configured to produce an ion intensity signal that is proportional tothe number of ions that reach, and are detected by, the ion detector 16.The ion intensity signal is supplied to the control circuit 18, whichthen processes the ion intensity signal to produce ion mobility spectralinformation. The memory unit 20 has instructions stored therein that areexecutable by the control circuit 18 to control the operation of thevarious electric field activation sources, V₁-V_(M).

In the embodiment illustrated in FIG. 1, the drift tube 14 ispartitioned into a plurality of cascaded drift tube segments beginningwith a first drift tube segment positioned adjacent to the ion source 12and defining the ion inlet of the drift tube 14, and ending with an Nthdrift tube segment defining the ion outlet of the drift tube 14. Ionsgenerated by the ion source 12 enter the ion inlet of the drift tube 14,and the electric field activation sources, V₁-V_(M), are operated suchthat the electric fields, i.e., drift fields, established in the variousdrift tube segments are modulated at a frequency that allows only ionshaving mobilities that are resonant with the operating conditions todrift through all of the various drift tube segments. In this way, theion mobility spectrometer 10 operates as an ion mobility filter thatfilters out or away all ions except those having ion mobilities that arewithin a specified range of ion mobilities defined by the frequency ofoperation of the electric field activation sources, V₁-V_(M).Additionally, ions drift through the various drift tube segments atfrequencies that are overtones of the frequency of operation of theelectric field activation sources, V₁-V_(M). Thus, the ion mobilityspectrometer 10 may be operated, as will be described in detail herein,to filter away all ions except those having ion mobilities that areresonant with a fundamental frequency, f_(f), and/or associated overtonefrequencies, of operation of the electric field activation sources,V₁-V_(M). Because of the ability to selectively transmit ions indifferent frequency regions, including those associated with higherovertones, the techniques described herein may be referred to asOvertone Mobility Spectrometry (OMS). In this document, the terms“harmonics” should be understood to include the fundamental frequency,f_(f), and integer multiples of the fundamental frequency, and the term“overtone” should be understood to include only the integer multiples ofthe fundamental frequency, f_(f).

Referring now to FIG. 2, a diagram is shown of one illustrativeembodiment of a portion of the drift tube 14 along with one illustrativearrangement of the electric field activation sources of the ion mobilityspectrometer 10 of FIG. 1. In the illustrated embodiment, the drift tube14 is partitioned into a number, N, of cascaded segments, S₁-S_(N),where N may be any positive integer greater than 2, and segments S₁-S₅are shown in FIG. 2. Each of the segments, e.g., S₁-S₅, isillustratively constructed of five concentric, electrically conductiverings, 30 ₁-30 ₅, each separated by a concentric, electricallyinsulating ring 32 ₁-32 ₄ (illustrated in FIG. 2 for the segment S₁only). The first electrically conductive ring, 30 ₁, of each segmentdefines an ion inlet gate, G_(I), to the segment, and the lastelectrically conductive ring, 30 ₅, of each segment defines an ionoutlet gate, G_(O), of the segment. Illustratively, the first and lastrings 30 ₁ and 30 ₅ contain mesh grids, e.g., 90% transmittance Ni meshgrid, although this disclosure contemplates embodiments which do notinclude one or both of the rings 30 ₁ and 30 ₅. In any case, adjacentones of the electrically conductive rings, 30 ₁-30 ₅, are separated byone of the electrically insulating rings, 32 ₁-32 ₄, and adjacentsegments, S₁-S_(N), of the drift tube 14 are separated by a concentric,electrically insulating isolator ring 34, e.g., Teflon®, a syntheticfluoropolymer resin. All of the rings, 30 ₁-30 ₅, 32 ₁-32 ₄ and 34 arestacked together, sealed with O-rings and compressed using a number,e.g., eight, of threaded rods, e.g., nylon. The segments, S₁-S_(N), arethen joined together to form the drift tube 14.

In the illustrated embodiment, a resistor, R, is electrically connectedbetween each of the electrically conductive rings in each drift tubesegment, and a resistor R_(E) is connected between the ion outlet gateand ion inlet gate of each adjacent drift tube segment. The drift tube14 of the ion mobility spectrometer instrument 10 is constructed withthe electrically conductive rings 30 ₁-30 ₅ electrically insulated fromeach other and with the drift tube segments S₁-S_(N) also electricallyisolated from each other so that electric fields can be developedseparately and independently in each of the segments S₁-S_(N) and/or ingroups of the segments S₁-S_(N). By applying suitable voltages acrossthe drift tube segments and/or groups of drift tube segments, as will bedescribed in greater detail hereinafter, uniform electric fields areillustratively established in each drift tube segment in a manner thattransmits ions generated by the ion source 12 through the drift tube 14and through the ion outlet of the last segment S_(N).

The region between the ion inlet gate and the ion outlet gate of eachdrift tube segment defines an ion transmission region of distance,d_(t), and the region between the ion outlet gate of one drift tubesegment and the ion inlet gate of the next adjacent drift tube segmentdefines an ion elimination region of distance, d_(e). Thus, for example,the drift tube segment S₁ has an ion transmission region of distance,d_(t)(1) defined between G_(I1) and G_(O1), and an ion eliminationregion of distance d_(e)(1) defined between G_(O1) and G_(I2).

In one example embodiment, the drift tube 14 is constructed of 21identical drift tube segments as just described, with an ion focusingfunnel (not shown) positioned approximately mid way between the ioninlet and the ion outlet of the drift tube 14. In this exampleembodiment, the ion transmission region, d_(t), and the ion eliminationregion, d_(e), are together 5.84 cm in length, and the total length ofthe 22-section drift tube 14 is 128.5 cm from the ion inlet to the ionoutlet of the drift tube 14. Further details relating to this exampleconstruction of the drift tube 14, including construction of the ionfocusing funnel, are provided in co-pending U.S. Patent Application Pub.No. US 2007/0114382 A2, the disclosure of which is incorporated hereinby reference. It will be understood, however, that this disclosurecontemplates other embodiments in which the drift tube 14 is constructedin accordance with other conventional techniques, portions or theentirety of which may be linear or non-linear. For example, the drifttube 14 may alternatively be provided in the form of a circular orcyclotron drift tube, and further details relating to some examplecircular or cyclotron drift tube arrangements are provided in co-pendingPCT Publication No. WO 2008/028159 A2, filed Aug. 1, 2007, thedisclosure of which is incorporated herein by reference. It will beunderstood, however, that in any such alternate configuration the drifttube will define a number of cascaded drift tube sections such thatelectric fields may be selectively and separately created in individualand/or groups of the drift tube sections.

In the embodiment illustrated in FIG. 2, one illustrative arrangement 40of the electric field activation sources, V₁-V_(M), is shown thatincludes two electric field activation sources, V₁ and V₂, electricallyconnected to the drift tube 14. The control circuit 18 is illustrativelyconfigured to control operation of the electric field activationsources, V₁ and V₂, e.g., in accordance with instructions stored in thememory 20 that are executable by the control circuit 18, in analternating fashion to generate electric fields within the drift tubesegments, S₁-S_(N), which cause ions of a specified range of ionmobilities to drift through the drift tube 14.

In the illustrated embodiment, the electric field activation sources V₁and V₂ are both conventional DC voltage sources that are controllable bythe control circuit 18 to produce a desired DC voltage across the + and− terminals. The + terminals of V₁ and V₂ are both electricallyconnected to the ion inlet gate, G_(I1), of the first drift tubesegment, S₁. The + terminal of V₁ is further electrically connected tothe ion inlet gates of the even-numbered drift tube segments, e.g., tothe ion inlet gate, G_(I2) of the second drift tube segment, S₂, the ioninlet gate, G_(I4), of the fourth drift tube segment, S₄, etc., andthe + terminal of V₂ is further electrically connected to the ion inletgates of the odd-numbered drift tube segments, e.g., to the ion inletgate, G_(I3) of the third drift tube segment, S₃, the ion inlet gate,G_(I5), of the fifth drift tube segment, S₅, etc. The − terminal of V₁is electrically connected to the ion outlet gates of the odd-numbereddrift tube segments, e.g., to the ion outlet gates, G_(O1), G_(O3),G_(O5), etc. of the drift tube segments S₁, S₃, S₅, etc., respectively.The − terminal of V₂ is electrically connected to the ion outlet gatesof the even-numbered drift tube segments, e.g., to the ion outlet gates,G_(O2), G_(O4), G_(O6), etc. of the drift tube segments S₂, S₄, S₆,etc., respectively. With the exception of V₁ connected across the ioninlet and ion outlet gates, G_(I1) and G_(O1) of the first drift tubesegment, S₁, V₁ and V₂ are thus connected across the ion inlet andoutlet gates of alternating, adjacent pairs of drift tube segments. Forexample, V₂ is electrically connected across S₁ and S₂, e.g., betweenG_(I1) and G_(O2), V₁ is electrically connected across S₂ and S₃, e.g.,between G_(I2) and G_(O3), V₂ is electrically connected across S₃ andS₄, e.g., between G_(I3) and G_(O4), etc.

As illustrated in FIG. 2, the voltage sources, V₁ and V₂, whenactivated, produce linear voltage gradients, VG₁ and VG₂ respectively,across the drift tube segments to which they are connected. Equal-valuedresistors, R, are electrically connected across adjacent pairs of theelectrically conductive rings, 30 ₁-30 ₅, of each drift tube segment,S₁-S_(N), and equal-valued resistors, R_(E), are connected between theion outlet gates and ion inlet gates of adjacent pairs of drift tubesegments. The value of R_(E) is selected relative to R (or vice versa)such that the linear voltage gradients, VG₁ and VG₂, establishcorresponding, constant-valued electrical fields across the variousdrift tube segment pairs.

The control circuit 18 is configured to control operation of the voltagesources, V₁ and V₂, by periodically switching one voltage source, V₁,V₂, on while the other voltage source, V₁, V₂, is off. This has theeffect of alternately establishing a constant electric field acrosssequential, cascaded pairs of the drift tube segment, S₁-S_(N). Thisgenerally allows only ions having ion mobilities that match theswitching frequency to traverse each cascaded pair of drift tubesegments. The periodic switching between V₁ and V₂ also establishes arepulsive electric field, i.e., an electric field that is oriented torepel ions traveling in a direction toward the ion detector 16, in theion elimination regions, d_(e), that follow each cascaded pair of drifttube segments. To illustrate this repulsive electric field, consider thecase when V₁ is off and V₂ is on so that only the voltage gradients VG₂of FIG. 2 exist. Ions entering the first drift tube segment S₁ willdrift under the constant electric field established by VG₂ while V₂ ison. However, ions that reach G_(O2) while V₂ is still on will befiltered out by the repulsive electric field, e.g., reverse electricfield, established between the high +V₂ potential at the ion inlet gateG_(I3) and the low −V₂ potential at the ion outlet gate G_(O2).Generally, V₂ establishes, when activated, repulsive electric fields inthe ion elimination regions d_(e) between the ion outlet gates ofeven-numbered drift tube segments and the ion inlet gates of the nextsequential, odd-numbered drift tube segments, and V₁ likewiseestablishes, when activated, identical repulsive electric fields in theion elimination regions d_(e) between the ion outlet gates ofodd-numbered drift tube segments and the ion inlet gates of the nextsequential, even-numbered drift tube segments. This periodic traversalof two drift tube segments and ion elimination in the activated ionelimination regions, d_(e), causes only ions having ion mobilities thatdrift in the established electric fields at the rate defined by the V₁,V₂ switching rate and overtones thereof to drift through the length ofthe drift tube 14 to the ion detector 16. Generally, if the switchingrate between V₁ and V₂ is constant, this switching rate defines afundamental frequency, f_(f), at which ions of a corresponding range ofmobilities can travel progressively through the drift tube segmentsS₁-S_(N). Alternatively or additionally, if the switching rate is sweptover a range of switching rates, ions having the corresponding range ofion mobilities will also travel progressively through the drift tubesegments S₁-S_(N) at overtone frequencies of the fundamental frequency,f_(f).

Referring now to FIG. 3, a number of plots A-F are shown demonstratingthe progression of ions through the first five segments, S₁-S₅ of thedrift tube 14 of FIGS. 1 and 2 when the voltage sources V₁ and V₂ arealternatively switched on and off. In the example illustrated in FIG. 5,the ion source 12 is configured to continually produce ions 50. Plot Aillustrates the condition when V₁ and V₂ are both initially off. Plot Billustrates the condition when V₁ is subsequently turned on while V₂remains off, which establishes a constant-valued electric field, E₁, inthe ion transmission regions d_(f) of each of the drift tube segments,S₁-S₅, and also in the even-numbered ion elimination regions d_(e)(2)and d_(e)(4), and which establishes a repulsive electric field in theodd-numbered ion elimination regions d_(e)(1), d_(e)(3) and d_(e)(5). Aportion 51 of the continually generated ions 50 drift through d_(f)(1)under the influence of the electric field E₁ toward d_(t)(2). However,ions that arrive at the ion elimination region d_(e) (1) before V₁ isswitched off are filtered out of the ions 51 by the repulsive fieldestablished in the ion elimination region d_(e)(1) by V₁. It will beunderstood that the voltage applied by V₁ across the first drift tubesegment, S₁, will be different than that applied across remaining pairsof the drift tube segments as illustrated in FIG. 2. Generally, thevoltage applied by V₁ across the first drift tube segment, S₁, will beselected so as to establish an electric field, E₁, in the iontransmission region d_(f)(1) that is identical to the electric field E₁established across various pairs of the remaining drift tube segments,S₂-S_(N).

Plot C illustrates the condition when V₁ is switched off and V₂ isswitched on, which establishes a constant-valued electric field, E₂(E₂=E₁), in the ion transmission regions d_(t) of each of the drift tubesegments, S₁-S₅, and also in the odd-numbered ion elimination regionsd_(e)(1), d_(e)(3) and d_(e)(5), and which establishes a repulsiveelectric field in the even-numbered ion elimination regions d_(e)(2) andd_(e)(4). The portion of ions 51 in the d_(t)(1) region continues toadvance under the influence of the electric field E₂ through d_(t)(2)toward d_(t)(3), and another portion 52 of the continually generatedions 50 drifts through d_(t)(1) under the influence of the electricfield E₂ toward d_(t)(2). Ions that arrive at the ion elimination regiond_(e)(2) before V₂ is switched off are filtered out of the ions 51 bythe repulsive field established in the ion elimination region d_(e)(2)by V₂.

Plot D illustrates the condition when V₂ is switched off and V₁ isswitched back on, which establishes the constant-valued electric fieldE₁ as described with respect to plot B. The portion of ions 51 in thed_(t)(2) region continues to advance under the influence of the electricfield E₁ through d_(t)(3) toward d_(t)(4), and another portion 53 of thecontinually generated ions 50 drifts through d_(t)(1) under theinfluence of the electric field E₁ toward d_(t)(2). However, the ions 52that were previously in the d_(t)(1) region are filtered away by therepulsive electric field established in the ion elimination regiond_(e)(1) and therefore do not advance to d_(t)(2), and ions that arriveat the ion elimination regions d_(e)(1) and d_(e)(3) before V₁ isswitched off are filtered out of the ions 53 and 51 respectively by therepulsive field established in the ion elimination regions d_(e)(1) andd_(e)(3) respectively.

Plot E illustrates the condition when V₁ is again switched off and V₂ isswitched back on, which establishes the constant-valued electric field,E₂ described with respect to plot C. The portion of ions 51 in thed_(t)(3) region continues to advance under the influence of the electricfield E₂ through d_(t)(4) toward d_(t)(5), the portion of ions 53 in thed_(t)(1) region continues to advance under the influence of the electricfield E₂ through d_(t)(2) toward d_(t)(3), and yet another portion 54 ofthe continually generated ions 50 drifts through d_(t)(1) under theinfluence of the electric field E₂ toward d_(t)(2). Ions that arrive atthe ion elimination regions d_(e)(2) and d_(e)(4) before V₂ is switchedoff are filtered out of the ions 53 and 51 respectively by the repulsivefield established in the ion elimination regions d_(e)(2) and d_(e)(4)respectively.

Plot F illustrates the condition when V₂ is again switched off and V₁ isswitched back on, which establishes the constant-valued electric fieldE₁ as described with respect to plot B. The portion of ions 51 in thed_(t)(4) region continues to advance under the influence of the electricfield E₁ through d_(t)(5) toward the next drift tube segment (S₆), theportion of ions 53 in the d_(t)(2) regions continues to advance underthe influence of the electric field E₁ through d_(t)(3) toward d_(t)(4),and yet another portion 55 of the continually generated ions 50 driftsthrough d_(t)(1) under the influence of the electric field E₁ towardd_(t)(2). The ions 54 that were previously in the d_(t)(1) region arefiltered away by the repulsive electric field established in the ionelimination region d_(e)(1) and therefore do not advance to d_(t)(2),and ions that arrive at the ion elimination regions d_(e)(3) andd_(e)(5) before V₁ is switched off are filtered out of the ions 53 and51 respectively by the repulsive fields established in the ionelimination regions d_(e)(3) and d_(e)(5) respectively.

While the embodiment of the drift tube 14 of FIG. 2 was illustrated anddescribed as including an arrangement 40 of electric field activationsources in the form of two DC voltage sources, V₁ and V₂, it will beunderstood that this disclosure is not so limited and that embodimentsare contemplated in which the arrangement of electric field activationsources includes more than two voltage sources. Referring now to FIGS.4A-4D, for example, a number of voltage gradient plots are shown, inrelation to the first eight cascaded segments, S₁-S₈, of the drift tube14, that illustrate alternative embodiments in which the arrangement ofelectric field activation sources include additional voltage sources. Asa reference, the voltage gradient plot 40 of FIG. 4B, illustrates theembodiment just described in which the arrangement of electric fieldactivation sources includes two voltage sources V₁ and V₂ connected andconfigured to produce the two illustrated voltage gradients VG₁ and VG₂.

The voltage gradient plot 60 of FIG. 4C, in contrast, illustrates anembodiment in which the arrangement of electric field activation sourcesincludes three voltage sources, V₁, V₂ and V₃, each illustrativelyidentical to the voltage sources V₁ and V₂ illustrated and describedwith respect to FIG. 2. In the embodiment of FIG. 4C, +V₁, +V₂ and +V₃are all electrically connected to the ion inlet gate G_(I1) of the firstdrift tube segment, S₁. The +V₁ is further electrically connected to theion inlet gates G_(I2), G_(I5) and G_(I8), of the drift tube segmentsS₂, S₅ and S₈ respectively, the +V₂ is further electrically connected tothe ion inlet gates G_(I3), and G_(I6), of the drift tube segments S₃and S₆ respectively, and the +V₃ is further electrically connected tothe ion inlet gates G_(I4), and G_(I4), of the drift tube segments S₄and S₇ respectively. The −V₁ is electrically connected to the ion outletgates G_(O1), G_(O4) and G_(O7), the −V₂ is electrically connected tothe ion outlet gates G_(O2), G_(O5) and G_(O8), and the −V₃ iselectrically connected to the ion outlet gates G_(O3) and G_(O6). In thethree voltage source arrangement, the voltage sources V₁-V₃ are thuselectrically connected, in alternating fashion, across three consecutivedrift tube segments with all three voltage sources electricallyconnected to the ion inlet grid G_(I1) of the first drift tube segment,S₁, and then with V₁ electrically connected across S₁, S₂-S₄, and S₅-S₇,with V₂ electrically connected across S₁-S₂, S₃-S₅ and S₆-S₈ and with V₃electrically connected across S₁-S₃ and S₄-S₇.

In operation, the control circuit 18 controls the voltage sources V₁-V₃by sequentially switching one voltage source on for a specified durationwhile maintaining the other two voltage sources in their off state forthat duration. As illustrated in FIG. 4C, for example, the controlcircuit 18 turns on V₁ for the specified duration while maintaining V₂and V₃ in their off states, followed by turning off V₁ and turning on V₂while maintaining V₃ in its off state for the specified duration,followed by turning off V₂ and turning on V₃ while maintaining V₁ in itsoff state for the specified duration. The control circuit 18 repeats theabove process many times to cause ions having mobilities related to thevoltage source switching frequency to drift through the various drifttube segments. It will be understood that the voltage applied by V₁across the first drift tube segment, S₁, will be different than thatapplied by V₁ across remaining triplets of the drift tube segments, andthat the voltage applied by V₂ across the first two drift tube segments,S₁-S₂, will also be different than that applied by V₂ across remainingtriplets of the drift tube segments. Generally, the voltage applied byV₁ across the first drift tube segment, S₁, will be selected so as toestablish an electric field, E₁, in the ion transmission region d_(t)(1)that is identical to the electric field E₁ established by V₁ acrossvarious triplets of the remaining drift tube segments, S₂-S_(N), and thevoltage applied by V₂ across the first two drift tube segment, S₁-S₂,will be selected so as to establish an electric field, E₂, in the iontransmission region d_(t)(1), ion elimination region d_(e)(1) and iontransmission region d_(t)(2) that is identical to the electric field E₂established by V₂ across various triplets of the remaining drift tubesegments, S₃-S_(N).

The voltage gradient plot 70 of FIG. 4D illustrates an embodiment inwhich the arrangement of electric field activation sources includes fourvoltage sources, V₁, V₂, V₃ and V₄, each illustratively identical to thevoltage sources V₁ and V₂ illustrated and described with respect to FIG.2. In the embodiment of FIG. 4D, +V₁, +V₂, +V₃ and +V₄ are allelectrically connected to the ion inlet gate G_(I1) of the first drifttube segment, S₁. The +V₁ is further electrically connected to the ioninlet gates G_(I2) and G_(I6), of the drift tube segments S₂ and S₆respectively, the +V₂ is further electrically connected to the ion inletgates G_(I3), and G_(I7), of the drift tube segments S₃ and S₇respectively, the +V₃ is further electrically connected to the ion inletgates G_(I4), and G_(I8), of the drift tube segments S₄ and S₈respectively, and the +V₄ is further electrically connected to the ioninlet gate G_(I5) of the drift tube segment S₅. The −V₁ is electricallyconnected to the ion outlet gates G_(O1) and G_(O5), the −V₂ iselectrically connected to the ion outlet gates G_(O2) and G_(O6), the−V₃ is electrically connected to the ion outlet gates G_(O3) and G_(O7),and the −V₄ is electrically connected to the ion outlet gates G_(O4) andG_(O8). In the four voltage source arrangement, the voltage sourcesV₁-V₄ are thus electrically connected, in alternating fashion, acrossfour consecutive drift tube segments with all four voltage sourceselectrically connected to the ion inlet grid G_(I1) of the first drifttube segment, S₁, and then with V₁ electrically connected across S₁,S₂-S₅, and S₆-S₉, with V₂ electrically connected across S₁-S₂ and S₃-S₆,with V₃ electrically connected across S₁-S₃ and S₄-S₇, and with V₄electrically connected across S₁-S₄ and S₅-S₈.

In operation, the control circuit 18 controls the voltage sources V₁-V₄by sequentially switching one voltage source on for a specified durationwhile maintaining the other three voltage sources in their off state forthat duration. As illustrated in FIG. 4D, for example, the controlcircuit 18 turns on V₁ for the specified duration while maintaining V₂,V₃ and V₄ in their off states, followed by turning off V₁ and turning onV₂ while maintaining V₃ and V₄ in their off states for the specifiedduration, followed by turning off V₂ and turning on V₃ while maintainingV₁ and V₄ in their off states for the specified duration, followed byturning off V₃ and turning on V₄ while maintaining V₁ and V₂ in theiroff states for the specified duration. The control circuit 18 repeatsthe above process many times to cause ions having mobilities related tothe voltage source switching frequency to drift through the variousdrift tube segments. It will be understood that the voltage applied byV₁ across the first drift tube segment, S₁, will be different than thatapplied by V₁ across remaining quadruplets of the drift tube segments,the voltage applied by V₂ across the first two drift tube segments,S₁-S₂, will be different than that applied by V₂ across remainingquadruplets of the drift tube segments, and the voltage applied by V₃across the first three drift tube segments, S₁-S₃, will be differentthan that applied by V₃ across remaining quadruplets of the drift tubesegments. Generally, the voltage applied by V₁ across the first drifttube segment, S₁, will be selected so as to establish an electric field,E₁, in the ion transmission region d_(t)(1) that is identical to theelectric field E₁ established by V₁ across various quadruplets of theremaining drift tube segments, S₂-S_(N), the voltage applied by V₂across the first two drift tube segment, S₁-S₂, will be selected so asto establish an electric field, E₂, in the ion transmission regiond_(t)(1), ion elimination region d_(e)(1) and ion transmission regiond_(t)(2) that is identical to the electric field E₂ established by V₂across various quadruplets of the remaining drift tube segments,S₃-S_(N), and the voltage applied by V₃ across the first three drifttube segment, S₁-S₃, will be selected so as to establish an electricfield, E₃, in the ion transmission regions d_(t)(1), d_(t)(2) andd_(t)(3) and in the ion elimination regions d_(e)(1) and d_(e)(2) thatis identical to the electric field E₃ established by V₃ across variousquadruplets of the remaining drift tube segments, S₄-S_(N).

The number of electric field activation sources, e.g., voltage sources,used in any particular embodiment, and the manner in which they areelectrically connected to the various drift tube segments to operate asdescribed above, is referred to as the phase (φ) of the ion mobilityspectrometer 10. In the example of FIGS. 2, 3 and 4B in which twovoltage sources V₁ and V₂ are used as described above, φ=2 as indicatedin the plot 40 of FIG. 4B. In the example of FIG. 4C in which threevoltage sources V₁, V₂ and V₃ are used as described above, φ=3 asindicated in the plot 60 of FIG. 4C. In the example of FIG. 4D in whichfour voltage sources V₁, V₂, V₃ and V₄ are used as described above, φ=4as indicated in the plot 70 of FIG. 4D. It will be noted from FIG. 3that in a φ=2 system, the fill rate of ions in the various drift tubesegments S₁-S_(N), i.e., the duty cycle of the ion mobility spectrometer10, is 50%. It can be shown that in a φ=3 system, the duty cycle of theion mobility spectrometer is 66.67% and in a φ=4 system, the duty cycleof the ion mobility spectrometer is 75%. A general expression for theduty cycle, d, of the ion mobility spectrometer 10 as a function of thephase, φ, is thus d=1−(1/φ).

Referring again to FIG. 3, the electric fields in the drift tube 14 in atwo-phase (φ=2) ion mobility spectrometer 10 are established by twosource V₁ and V₂. The electric fields established in the drift tube 14by activation of V₁ include an electric drift field E₁, i.e., anelectric field through which ions generated by the ion source drifttoward the ion detector 16, in each of the drift tube segments, i.e., ineach of the ion transmission regions d_(t), and also in theeven-numbered ion elimination regions, d_(e)(2), d_(e)(4), etc., andalso includes a repulsive electric field, i.e., an electric field thatrepels and filters away ions traveling in the direction of the electricdrift field, in odd-numbered ion elimination regions, d_(e)(1),d_(e)(3), d_(e)(5), etc. Similarly, the electric fields established inthe drift tube 14 by activation of V₂ includes an electric drift fieldE₂ in each of the drift tube segments and also in the odd-numbered ionelimination regions, d_(e)(1), d_(e)(3), d_(e)(5), etc., and alsoincludes a repulsive electric field in even-numbered ion eliminationregions, d_(e)(2), d_(e)(4), etc.

It can be shown that in three-phase systems (φ=3) that include threeelectric field activation sources, V₁-V₃, such as that illustrated inFIG. 4C, activation of V₁ establishes a repulsive electric field in thefirst ion elimination region, d_(e)(1), and in every following 3^(rd)ion elimination region, d_(e)(4), d_(e)(7), d_(e)(10), etc., and alsoestablishes an electric drift field, E₁, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Activation of V₂ likewise establishes a repulsive electric field in thesecond ion elimination region, d_(e)(2), and in every following 3^(rd)ion elimination region, d_(e)(5), d_(e)(8), d_(e)(11), etc., and alsoestablishes an electric drift field, E₂, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Activation of V₃ similarly establishes a repulsive electric field in thethird ion elimination region, d_(e)(3), and in every following 3^(rd)ion elimination region, d_(e)(6), d_(e)(90, d_(e)(12), etc., and alsoestablishes an electric drift field, E₃, in all remaining ionelimination regions and in all of the drift tube segments d_(t).

It can also be shown that in four-phase systems (φ=4) that include fourelectric field activation sources, V₁-V₄, such as that illustrated inFIG. 4D, activation of V₁ establishes a repulsive electric field in thefirst ion elimination region, d_(e)(1), and in every following 4^(th)ion elimination region, d_(e)(5), d_(e)(9), d_(e)(13), etc., and alsoestablishes an electric drift field, E₁, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Activation of V₂ likewise establishes a repulsive electric field in thesecond ion elimination region, d_(e)(2), and in every following 4^(th)ion elimination region, d_(e)(6), d_(e)(10), d_(e)(14), etc., and alsoestablishes an electric drift field, E₂, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Activation of V₃ similarly establishes a repulsive electric field in thethird ion elimination region, d_(e)(3), and in every following 4^(th)ion elimination region, d_(e)(7), d_(e)(11), d_(e)(15), etc., and alsoestablishes an electric drift field, E₃, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Finally, activation of V₄ establishes a repulsive electric field in thefourth ion elimination region, d_(e)(4), and in every following 4^(th)ion elimination region, d_(e)(8), d_(e)(12), d_(e)(16), etc., and alsoestablishes an electric drift field, E₄, in all remaining ionelimination regions and in all of the drift tube segments d_(t).

From the foregoing examples, a generalized characterization can be madefor an M-phase system, i.e., one that includes a number, M, of electricfield activation sources, V₁-V_(M). In such an M-phase system, thenumber, M, of electric field activation sources are each be operativelyconnected to one or more of the plurality of drift tube segments suchthat, when activated, each establishes a repulsive electric field in atleast one of the first M ion elimination regions and in every followingMth ion elimination region, and also establishes an electric drift fieldin all remaining ion elimination regions and in all of the plurality ofcascaded drift tube segments. In operation, the control circuit 18sequentially activates each of the number, M, of electric fieldactivation sources for a time duration while deactivating the remainingnumber, M, of electric field activation sources a number of times tothereby cause only ions generated by the ion source that have apredefined ion mobility or range of ion mobilities to traverse the drifttube 14.

Transmission of ions through the various drift tube segments S₁-S_(N) asjust described is only possible if the mobilities of the ions are inresonance with the switching rates of the electric fields applied by theelectric field activation sources regardless of the phase of thespectrometer 10. In other words, to transmit ions sequentially throughthe various drift tube segments S₁-S_(N) as just described, the ionsmust have mobilities that allow traversal exactly one drift tube segmentin one field application duration. Ions with mobilities that are offresonance either traversing a drift tube segment too quickly or tooslowly are eventually eliminated in one of the ion elimination regionsd_(e). The frequency at which the various electric field activationsources are switched on/off, i.e., the frequency at which the ions haveresonant mobilities, is termed the fundamental frequency, f_(f).

In the above description of the operation of the ion mobilityspectrometer instrument 10, the control circuit 18 is described as beingconfigured to control operation of the electric field activation sourcesV₁-V_(M). Illustratively, the memory unit 20 has instructions storedtherein that are executable by the control circuit 18 to controloperation of the electric field activation sources V₁-V_(M) in thismanner.

In one alternative embodiment, each of the electric field activationsources V₁-V_(M) may be programmable to produce, when triggered by anadjacent, e.g., lower-numbered, one of the electric field activationsources V₁-V_(M), an electric field activation pulse of desiredduration. In this embodiment, each higher-numbered one of the electricfield activation sources V₁-V_(M) may be programmable to be triggeredfor activation by deactivation of an adjacent lower-numbered one of theelectric field activation sources V₁-V_(M). Thus, deactivation of V₁will trigger activation of V₂, deactivation of V₂ will triggeractivation of V₃ (or V₁ again), and so forth. In this embodiment, thecontrol circuit 18 is configured to control operation of the electricfield activation sources V₁-V_(M) only by activating the first one ofthe electric field activation sources V₁-V_(M).

In another alternative embodiment, each of the electric field activationsources V₁-V_(M) may be programmable to produce, when triggered by thecontrol circuit 18, an electric field activation pulse having desiredduration. In this embodiment, the control circuit 18 controls activationtimes of each of the electric field activation sources V₁-V_(M), andonce activated each of the electric field activation sources V₁-V_(M) isoperable to produce a pulse having time duration equal to a programmedpulse duration. In this embodiment, the control circuit 18 is configuredto control operation of the electric field activation sources V₁-V_(M)only by activating at specified times each of the electric fieldactivation sources V₁-V_(M).

It will be understood that while the electric field activation sources,V₁-V_(M) were described as producing DC voltages of programmableduration this disclosure contemplates embodiments in which the electricfield activation sources are configured to produce alternatively shapedelectric field activation pulses. For example, such alternatively shapedelectric field activation pulses may be linear or piece-wise linearpulse shapes, such as triangular or other linear or piece-wise linearshapes, or may be non-linear shapes such as sine-wave, Gaussian or othernon-linear shapes. The corresponding electric fields applied intime-dependent fashion to the various segments S₁-S_(N) of the drifttube 14 as described above may thus be linearly, piece-wise linearly ornon-linearly varying. Alternatively still, different ones and/or blocksof the electric field activation sources V₁-V_(M) may be activated fordifferent durations. Those skilled in the art will recognize that, ingeneral, any one or more of the segments S₁-S_(N) may be operated for aduration that is different than the duration of operation of any one ormore of the remaining ones of the segments S₁-S_(N), and that operationof the ion mobility instrument 10 in this manner will result in amulti-dimensional ion mobility spectrometer instrument, i.e., a drifttube having one or more segments in any location relative to the ioninlet and ion outlet that is/are tuned to pass therethrough only ionshaving a mobility or range of mobilities that is/are different thanthat/those of one or more of the remaining segments.

Referring now to FIG. 5, a flowchart is shown of one illustrativeembodiment of a process 80 for operating the ion mobility spectrometerinstrument 10 to act as an ion mobility filter by allowing travelthrough the drift tube 14 of only ions having a predefined mobility orrange of mobilities as described hereinabove with respect to FIGS. 1-4D.The process 80 illustrated in FIG. 5 may be provided, in whole or inpart, in the form of instructions that are stored in the memory unit 20of the control circuit 18 and that are executable by the control circuit18 to control the ion mobility spectrometer instrument 10 in accordancewith the process 80. The process 80 begins at step 82 where the drifttime, DT, through the drift tube 14 is determined for the samplecomponent of interest. This may be done, for example, by first operatingthe ion drift tube 14 in a conventional manner to determine the drifttime, DT, of the sample component of interest, although otherconventional techniques may be used at step 82 to determine the drifttime, DT, of the sample component of interest. For example, conventionalion mobility spectrometer configurations could be used to determine adrift time, or a drift time could be retrieved from literature, althoughin either case, instrument operating parameters used to determine suchdrift times, e.g., buffer gas pressure, operating temperature, drifttube length, etc., would have to be taken into account to determinecorresponding operating parameters for those of the ion mobilityspectrometer 10. Referring to FIG. 6, a plot 94 of ion intensity vs.drift time is shown illustrating the drift time of ions of the sodiatedmonomer [M+Na]⁺ form of the simple oligosaccharide isomer raffinosethrough one particular embodiment of the ion mobility spectrometer 10.In this embodiment, the drift time, DT, of raffinose through the drifttube 14 is approximately 15.8 ms.

Following step 82, the pulse width, PW, of the number of electric fieldactivation sources V₁-V_(M) used in the ion mobility spectrometerinstrument 10 is computed at step 84. The pulse width, PW, is theduration of the electric field that will be applied by each of theelectric field activation sources V₁-V_(M) to pass the sample componentof interest, e.g., raffinose, through each segment. In order to pass thesample component of interest through a drift tube 14 having N segments,the pulse width, PW, must therefore satisfy the relationship PW=DT/N.

Following step 84, the shape of the pulse width is selected at step 86,and thereafter at step 88 the peak voltage of the electric fieldactivation sources V₁-V_(M) is selected. The process 80 advances fromstep 88 to step 90, and simultaneously with step 90 the ion sourcevoltage supply, V_(IS), is controlled at step 92 in a manner that causesthe ion source 12 to produce ions. The ions produced at step 92 may beproduced continuously or may instead be produced discretely as describedhereinabove. In any case, the control circuit 18 is operable at step 90to control the electric field activation sources V₁-V_(M), as describedhereinabove, to sequentially apply electric fields having the selectedshape, duration and peak field strength to the various drift tubesegments, S₁-S_(N) as described hereinabove by example with reference toFIGS. 2-4D. Steps 90 and 92 may be repeated continuously or a finitenumber of times to thereby operate the ion mobility spectrometerinstrument 10 as a continuous or discrete ion mobility filter. For theraffinose sample illustrated in FIG. 6, the pulse width, PW, of theelectric field activation sources V₁-V_(M) in the ion mobilityspectrometer instrument 10 of FIG. 1, in which the drift tube 14 isconstructed of 20 drift tube segments, S₁-S₂₀, and one ion focusingfilter positioned approximately mid way between the ion inlet and ionoutlet of the drift tube 14, is approximately 500 microseconds, whichcorresponds to an electric field activation source switching frequencyof approximately 2.0 kHz. It will be understood that steps 82-88 are notrequired to be executed in the illustrated order, and that one or moreof these steps may alternatively be interchanged with one or more otherof these steps.

In addition to operation of the ion mobility spectrometer instrument 10as an ion mobility filter as illustrated and described herein, the ionmobility spectrometer instrument 10 may also be operated in a mannerthat transmits ions at overtone frequencies of the fundamentalfrequency, f_(f), as described briefly above. Referring to FIG. 7, forexample, a flowchart of an illustrative process 100 for operating theion mobility spectrometer 10 by sweeping the pulse widths, PW, of theelectric field activation sources, V₁-V_(M), over a range of pulse widthdurations. In addition to producing a fundamental ion intensity peakthat corresponds to ion intensity peak resulting from the process 80 ofFIG. 5, the process 100 further produces overtone ion intensity peaksthat may be analyzed in the frequency domain to reveal additionalcharacteristics of the sample component of interest. The process 100illustrated in FIG. 7 may be provided, in whole or in part, in the formof instructions that are stored in the memory unit 20 of the controlcircuit 18 and that are executable by the control circuit 18 to controlthe ion mobility spectrometer instrument 10 in accordance with theprocess 100.

The process 100 begins at step 102 where initial and final pulse widthdurations, PW_(I) and PW_(F) respectively, and a ramp rate, R (or stepsize), are selected. Illustratively, the initial pulse width duration,PW_(I), may be selected to be slightly longer than necessary to producethe fundamental ion intensity peak so that the resulting ion intensityvs. frequency spectrum begins approximately at the fundamental peak.Illustratively, the final pulse width duration, PW_(F), may be selectedto be a frequency beyond which no useful information is expected tooccur, or beyond which no ion intensity information is sought. In anycase, the ramp rate, R, and/or frequency step size between the initialand final pulse width durations, PW_(I) and PW_(F), will typically beselected to provide sufficient time at each pulse width duration toextract useful information from the ion mobility spectrometer instrument10. Such information can be of the form of ion collision cross sections,Ω, which can be derived from OMS measurements according to the followingequation:

${\Omega = {\frac{\left( {18\;\pi} \right)^{1/2}}{16}{\frac{ze}{\left( {k_{b}T} \right)^{1/2}}\left\lbrack {\frac{1}{m_{I}\;} + \frac{1}{m_{B}}} \right\rbrack}^{1/2}\frac{E\left\lbrack {{\phi\left( {h - 1} \right)} + 1} \right\rbrack}{f\left( {d_{t} + d_{e}} \right)}\frac{760}{P}\frac{T}{273.2}\frac{1}{N}}},$where ze is ion charge, k_(b) is Boltzmann's constant, P and Tcorrespond to the buffer gas pressure and temperature respectively, N isthe neutral number density, E is the electric field, f is the fieldapplication frequency, the quantity φ(h−1)+1 is the harmonic number orovertone number, m_(I) and m_(B) correspond to the mass of the ion andthe mass of the buffer gas, respectively, and all other variables havebeen defined herein.

Following step 102, the shape of the pulse width is selected at step104, and thereafter at step 106 the peak voltage of the electric fieldactivation sources V₁-V_(M) is selected. The process 100 advances fromstep 106 to step 108, and simultaneously with step 108 the ion sourcevoltage supply, V_(IS), is controlled at step 110 in a manner thatcauses the ion source 12 to produce ions. The ions produced at step 110may be produced continuously or may instead be produced discretely asdescribed hereinabove, although if produced discretely a timingmechanism will typically be required to trigger new supplies of ionscoincident with the changing of the pulse width durations. In any case,the control circuit 18 is operable at step 108 to control the electricfield activation sources V₁-V_(M), as described hereinabove, to applyelectric fields having the selected shape and peak field strength to thedrift tube segments, S₁-S_(N) while sweeping the pulse width duration,PW, between PW_(I) and PW_(F) at the selected ramp rate and/or stepsize. It will be understood that steps 102-106 are not required to beexecuted in the illustrated order, and that one or more of these stepsmay alternatively be interchanged with one or more other of these steps.

While not specifically illustrated in FIG. 7 as a step in the process100, ion detection signals produced by the ion detector 16 may beprocessed by the control circuit 18 and converted to the frequencydomain in a conventional manner for further analysis and/or observation.For the raffinose sample illustrated in FIG. 6, for example, sweepingthe pulse width, PW, of the electric field activation sources V₁-V₄ inthe ion mobility spectrometer instrument 10 of FIG. 1 betweenapproximately 10 milliseconds down to approximately 22 micro-secondsyields the ion intensity vs. frequency spectrum 112 illustrated in FIG.8. Illustratively, the 3^(rd) overtone produces the most highly resolvedion intensity peak.

Generally, the overtones produced by frequency sweeps of the typeillustrated in FIG. 8 will be defined, at least in part, by the phase(φ) of the ion mobility spectrometer 100. Referring to FIG. 9, forexample, a number of plots 120, 122, 124, 126 and 128 are shown offrequency spectrums of raffinose in which the phase, φ, of the ionmobility spectrometer 10 correspondingly increases. In all cases, theelectric field activation sources, V₁-V_(M) were configured to operateas described hereinabove with respect to FIGS. 2-4D. In the plot 120,φ=2, and the associated frequency spectrum includes an ion peak at thefundamental frequency, f_(f), and additional peaks at the third andfifth overtones. In the plot 122, φ=3, and the associated frequencyspectrum includes an ion peak at the fundamental frequency, f_(f), andadditional peaks at the fourth and seventh overtones. In the plots 124,126 and 128, φ=4, 5 and 6 respectively. The frequency spectrum 124includes an ion peak at the fundamental frequency, f_(f), and additionalpeaks at the fifth, ninth and thirteenth overtones, the frequencyspectrum 126 includes an ion peak at the fundamental frequency, f_(f),and additional peaks at the sixth, eleventh and sixteenth overtones, andthe frequency spectrum 128 includes an ion peak at the fundamentalfrequency, f_(f), and additional peaks at the seventh, thirteenth andnineteenth overtones. It should be noted that as the phase of the ionmobility spectrometer 10 is increased, secondary overtones increasingappear between the fundamental peak, f_(f), and the first expectedovertone. These secondary overtones correspond to intermediate harmonicfrequencies, i.e., those between the overtone frequencies, and may carryadditional ion information.

Generally, the overtones that should be expected to be observed inembodiments of the ion mobility spectrometer 10 operated with uniform,constant electric fields in the various drift tube segments, S₁-S_(N) asdescribed hereinabove, are given by the equation H=φ(h−1)+1, h=1, 2, 3,. . . , where H is a harmonic number, φ is the phase of the ion mobilityspectrometer 10, and h is an integer. Thus, for φ=2, H=1, 3, 5, 7, . . ., for φ=3, H=1, 4, 7, 10, . . . , for φ=4, H=1, 5, 9, 13, . . . , for(1)=5, H=1, 6, 11, 16, . . . , and for φ=6, H=1, 7, 13, 19, . . . , etc.

The resolving power, R, of the ion mobility spectrometer instrument 10is defined by the equation R_(OMS)=f/Δf, where f is the frequency atwhich maximum ion intensity of transmitted and Δf is the width of thepeak at half maximum. Generally, it is observed that the resolvingpower, R, of the ion mobility spectrometer instrument 10 increases withincreasing overtone number, H. The resolving power, R, of the ionmobility spectrometer instrument 10 is also influenced by the totalnumber, N, of drift tube segments, S₁-S_(N), used. Referring to FIG. 10,for example, a number of plots 130 are shown illustrating the shapes offundamental-frequency, ion intensity peaks for a four-phase (φ=4) ionmobility spectrometer instrument 10 in which the total number of drifttube segments, N, is varied between 11 and 43 as indicated on the leftportion of FIG. 10. The plots 130 were generated from a sample of thesodiated monomer [M+Na]⁺ form of the simple oligosaccharide isomermelezitose using the ion mobility instrument 10 illustrated anddescribed herein. As illustrated in FIG. 10, whereas the peakintensities do not change significantly, the widths, Δf, of the peaks athalf maximum decrease as N increases. For example, Δf₁₁, correspondingto the width of the N=11 peak at half maximum, is approximately 1600 Hz,whereas Δf₄₃, corresponding to the width of the N=43 peak at halfmaximum, is approximately 345 Hz. The ratio f/Δf, and thus, R_(OMS),accordingly increases as the number, N, of drift tube segments S₁-S_(N)increases.

In a conventional ion mobility spectrometer; that is to say, an ionmobility spectrometer in which a single electric field is applied acrossthe length of the drift tube, the resolving power is generallyunderstood to follow the relationshipR_(IMS)=SQRT[(E*e*L)/(16*k_(b)*T*In2)], where E is the applied electricfield, e is the elementary charge value, L is the length of the drifttube, k_(b) is Boltzmann's constant, and T is the temperature of thedrift tube.

In the ion mobility instruments 10 illustrated and described herein, theoverall resolving power, R_(OMS), is a function of R_(IMS) and is also afunction of the total number, n, of drift tube segments, S₁-S_(N), thephase number, φ, of the applied electric field and the harmonic number,m. Illustratively, R_(OMS) is given by the equations:

$R_{OMS} = {\frac{1}{1 - {\left\lbrack {1 - \frac{C}{R_{IMS}}} \right\rbrack\left\lbrack \frac{{mn} - \left\lbrack {\phi - 1 - \frac{l_{e}}{l_{t} + l_{e}}} \right\rbrack}{mn} \right\rbrack}}\mspace{14mu}{or}}$$R_{OMS} = \frac{1}{{\frac{C}{R_{IMS}}\left\lbrack {1 - \frac{\phi - 1 - \frac{l_{e}}{l_{t} + l_{e}}}{mn}} \right\rbrack} + \frac{\phi - 1 - \frac{l_{e}}{l_{t} + l_{e}}}{mn}}$where C is a constant and all other variables have been defined herein.It should be noted that the resolving power, R_(OMS), generallyincreases with increasing n and also with increasing m, and theresolving power, R_(OMS), decreases with increasing φ. It should also benoted that in the limit of high R_(IMS), the first term in thedenominator of the foregoing equation approaches zero and the foregoingequation reduces to R_(OMS)=m*n/[φ−1−I_(e)/(I_(t)+I_(e))].

It can further be shown that the resolving power of any peak in an OMSdistribution can obtained by replacing the harmonic number, m, in theabove equation with (φq+1), and then by multiplying the entire equationby the quantity (φ/k+1), where k is an overtone series index havinglimits of 0 to φ−1, and q is an overtone peak index having limits of 0to infinity.

Referring now to FIG. 11, plots of ion intensity vs. frequency are shownto illustrate one implementation of the enhanced resolving power of theion mobility spectrometer 10 at overtone frequencies. The plots of FIG.11 are frequency-domain plots that were generated with a two-phase (φ=2)configuration of the ion mobility instrument 10. In the plots of FIG.11, only the overtone peaks 3 and 5 are shown along with the peak at thefundamental frequency, 1. The plot 140 represents a frequency-domainplot of raffinose, the plot 142 represents a frequency-domain plot ofthe sodiated monomer [M+Na]⁺ form of the simple oligosaccharide isomermelezitose, and the plot 144 represents a frequency-domain plot of a 3:1raffinose:melezitose mixture. The frequency spectrum of the plot 144illustrates that whereas the raffinose and melezitose areindistinguishable at the fundamental frequency, they are partiallyresolved at the third overtone, 146 ₁ and 146 ₂, and are fully resolvedat the fifth overtone, 148 ₁ and 148 ₂. The harmonic/overtone analysisdescribed in this disclosure, e.g., the pulse width duration sweepingprocess 100 illustrated in FIG. 7, may therefore be used to accuratelyidentify a sample component of interest, and/or to distinguish a samplecomponent of interest from another sample component.

The raffinose and melezitose mixture can alternatively be resolved at ornear their fundamental frequencies if allowed to drift along asufficiently long drift distance. This may be accomplished, for example,by employing the ion mobility spectrometer operating techniqueillustrated in FIG. 5 in an ion mobility spectrometer having a circularor so-called cyclotron geometry, as illustrated and described inco-pending PCT Publication No. WO 2008/028159 A2, filed Aug. 1, 2007,the disclosure of which has been incorporated herein by reference.Referring now to FIG. 12A, plots 150, 152 and 154 are shown of such anexperiment in which raffinose and melezitose were separated in acircular or cyclotron geometry ion mobility spectrometer 160 having acyclotron portion constructed such that the drift tube, made up ofcascaded ion transmission sections (d₁) and ion elimination sections(d_(e)) as illustrated and described hereinabove with respect to FIGS.2-4, defines a closed and continuous ion travel path.

Referring to FIG. 12B, one illustrative embodiment of such a cyclotronion mobility spectrometer 160 is shown. In the illustrated embodiment,the drift tube is made up of four conventional ion funnels, F2-F5 joinedat each end by curved drift tube segments D1-D4. Two of the curved drifttube segments D1 and D4 have Y-shaped geometries. In addition to formingone drift tube segment of the cyclotron portion of the drift tube, thesegment D1 selectively direct ions generated by an ion source, e.g., anelectrospray ion source, ESI, coupled to D1 via a funnel/gatearrangement, F1/G1, into the cyclotron portion via an ion entrance drifttube section. In addition to forming another drift tube segment of thecyclotron portion of the drift tube, the segment D4 selectively directsions via an ion exit drift tube segment from the cyclotron portion andthrough a cascaded funnel, F6, and drift tube segment, D5 to an iondetector, DET. It will be understood that the embodiment of thecyclotron ion mobility spectrometer 160 shown in FIG. 12B is merelyillustrative, and that the cyclotron portion of the spectrometer 160 mayalternatively include more or fewer drift tube segments than the eightsegments (D1-D4 and F2-F5) shown. It will further be understood thatwhile the ion entrance drift tube segment is shown coupled between theion source (ESI-F1/G1) and the drift tube segment D1, it mayalternatively be coupled to a different one of the drift tube segments.Likewise, while the ion exit drift tube segment is shown coupled betweenthe drift tube segment D4 and the funnel segment F6, it mayalternatively be coupled to a different one of the drift tube segments.Moreover, while the ion entrance and exit drift tube segments are showncoupled to different ones of the drift tube segments, they mayalternatively be coupled to a common one of the drift tube segments suchthat ions are admitted to and extracted from the same drift tubesegment. It will further be understood that more or fewer drift tubesegments and/or ion funnels may be positioned between the ion outlet ofthe ion exit drift tube segment of D4 and the ion detector, DET. In oneembodiment, for example, the ion detector, DET, may be coupled directlyto the ion outlet of the ion exit drift tube segment of D4, and in otherembodiments any number of drift tube segments and/or ion funnels may bepositioned between the ion exit drift tube segment of D4 and the iondetector, DET. In any case, the ion detector, DET, may be conventionaland is configured to detect ions exiting the ion drift tube segmentportion of D4 and produce corresponding ion detection signals. Thememory of the control circuit illustratively includes instructionsstored therein that are executable by the control circuit to process theion detection signals in a conventional manner to determine ion mobilityspectral information therefrom.

Although not specifically shown in FIG. 12B for ease of illustration andunderstanding, it will be understood that a number, M, of electric fieldactivation sources are connected to the various drift tube sections ofthe cyclotron ion mobility spectrometer 160, a voltage source, V_(IS),is connected to the ion source (ESI-F1/G1), a source of buffer gas isfluidly coupled to the drift tube, and a control circuit is electricallyconnected to one or more of the M electric field activation sources,voltage source, V_(IS) and ion detector, all as illustrated anddescribed herein with respect to FIGS. 1-4. The control circuit, asdescribed hereinabove, illustratively includes a memory havinginstructions stored therein that are executable by the control circuitto control operation of the cyclotron ion mobility spectrometer 160. Thevarious voltage sources and control circuitry, as illustrated anddescribed above, are thus omitted from FIG. 12B for brevity. The number,M, may be any positive integer greater than 2, and general operation ofthe number, M, of electric field activation sources is illustrated anddescribed herein with respect to FIGS. 1-4.

The ion source is illustrated in FIG. 12B as an electrospray ion sourcefluidly coupled to an ion funnel/gate, F1/G1, although the ion sourcemay alternatively be or include any conventional ion source that may becontrolled, via the voltage source, V_(IS), by the control circuitaccording to instructions stored in the memory that are executable bythe control circuit to selectively produce ions in a single, e.g.,one-shot, periodic, e.g., pulsed, and/or continuous fashion as is knownin the art. The ion gate, G1, of the ion source is illustrativelypositioned at an ion inlet of the ion entrance drift tube segment of D1such that the ion source is coupled to the inlet of the ion entrancedrift tube segment of D1, and an ion outlet of the ion entrance drifttube segment of D1 is coupled to the cyclotron portion of D1. The ionexit drift tube segment of D4 likewise has an ion inlet that is coupledto the cyclotron portion of D4, and an ion outlet coupled to the inletof the ion funnel F6.

The drift tube of the cyclotron ion mobility spectrometer 160illustrated in FIG. 12B is, like the embodiments illustrated in FIGS.1-4, partitioned into multiple cascaded drift tube segments D1-D4 andF2-F5. In one embodiment, each of the drift tube segments D1-D4 andF2-F5 has an ion inlet at one end and an ion outlet at an opposite end,and an ion elimination region is defined between the ion outlet and theion inlet of each adjacent drift tube segment as illustrated anddescribed hereinabove with respect to FIGS. 1-4. The ion outlet of alast one of the drift tube segments, e.g., F5, is coupled to the ioninlet of the first one of the drift tube segments, e.g., D1, such thatthe drift tube defines therein a closed and continuous ion travel pathwhich, in the illustrated embodiment, extends clockwise within D1-D4 andF2-F5. Illustratively, as just described, the ion elimination regionsmay be defined between the ion outlets and ion inlets of each of thedrift tube segments D1-D4 and F2-F5, such as illustrated in FIG. 2, andin this embodiment, each of D1-D4 and F2-F5 is an ion transmissionsection, d_(t), and the ion elimination regions, d_(e), are definedbetween adjacent ones of D1-D4 and F2-F5. In alternative embodiments,the lengths of the funnel sections F2-F5 may be made shorter than thelengths of the drift tube sections D1-D4, and in this embodiment, thedrift tube sections D1-D4 are the ion transmission sections, d_(t), andthe funnel sections F2-F5 are the ion elimination sections, d_(e). Inother alternative embodiments, the lengths of the drift tube sectionsD1-D4 may be made shorter than the lengths of the funnel sections F2-F5,and in this embodiment the funnel sections F2-F5 are the iontransmission sections, d_(t), and the drift tube sections D1-D4 are theion elimination sections.

An ion gate arrangement is positioned within the drift tube segment D4,and is configured to control ion travel through the cyclotron and ionexit drift tube portions of D4. The ion gate arrangement is generallyresponsive to one set of one or more ion gate signals produced by thecontrol circuit to direct ions moving through the drift tubes D1-D3 andF2-F5 through the cyclotron drift tube portion of D4 such that the ionsmay continue to travel around the cyclotron portion of the spectrometer160 defined by D1-D4 and F2-F5 while also blocking the ions fromentering the ion exit drift tube segment portion of D4 such that ionsmoving through the cyclotron drift tube segment portion of D4 cannotadvance to the ion detector, DET. The ion gate arrangement is alsogenerally responsive to another set of the one or more ion gate signalsproduced by the control circuit to direct ions moving through the drifttubes D1-D3 and F2-F5 through the ion exit drift tube segment portion ofD4 while also blocking ions from moving completely through the drifttube segment portion of D4 such that the ions travelling around thecyclotron portion of the spectrometer 160 defined by D1-D4 and F2-F5 donot advance completely through the drift tube segment portion of D4 andinstead advance through the ion exit drift tube segment portion of D4 tothe ion detector, DET. The ion gate arrangement is thus responsive tothe one set of one or more ion gate signals to direct ions travelingthrough the cyclotron portion of the spectrometer 160 to the next drifttube section, e.g., F5, in the cyclotron portion of the spectrometer160, and to the other set of one or more ion gate signals to extract theions traveling through the cyclotron portion of the spectrometer 160 bydirecting the ions through the ion exit drift tube section of D4 towardthe ion detector, DET. Illustratively, the ion mobility spectrometer 160includes one or more additional voltage sources electrically connectedto the ion gate arrangement, and the control circuit is thus generallyoperable to control the ion gate arrangement to direct ions movingthrough, and or blocking ions from moving through, the ion gatearrangement by controlling operation of such voltage sources in aconventional manner. The one or more additional voltage sources may beconventional voltage sources included within, or in addition to, thenumber, M, of electric field activation sources. Illustratively, thememory of the control circuit has instructions stored therein that areexecutable by the control circuit to control operation of the ion gatearrangement just described by controlling operation of the one or moreadditional voltage sources.

In the embodiment illustrated in FIG. 12B, the ion gate arrangement justdescribed is implemented in the form of two separate ion gates; G2apositioned in, or at the ion inlet of, the ion exit drift tube segmentportion of D4, and G2b positioned in the cyclotron drift tube segmentportion of D4. In this embodiment, the one set of the one or more iongate signals described above may include a first ion gate signal towhich the ion gate G2b is responsive to allow ions to pass therethroughand a second ion gate signal to which the ion gate G2a is responsive toblock ions from passing therethrough, and the other set of the one ormore ion gate signals described above may include a third ion gatesignal to which the ion gate G2b is responsive to block ions frompassing therethrough and a fourth ion gate signal to which the ion gateG2a is responsive to allow ions to pass therethrough. Those skilled inthe art will recognize that the ion gate arrangement may include more orfewer ion gates variously positioned relative to D4 and controllable bythe control circuit or other electronic controller to direct ionsthrough the cyclotron drift tube segment portion of D4 while blockingions from entering the ion exit drift tube segment portion of D4, and toalternatively direct ions through the ion exit drift tube segmentportion of D4 while blocking ions from traveling completely through thecyclotron drift tube segment portion of D4.

In the embodiment illustrated in FIG. 12B, ions are introduced into thecyclotron portion (e.g., D1-D4 and F2-F5) of the spectrometer 160 viacontrol of the gate, G1, such that ions enter the cyclotron portion viathe ion entrance drift tube segment portion of D1. With the ion gatesG2a and G2b set that G2b allows ions to pass therethrough and G2a blocksions from passing therethrough, ions are then directed around thecyclotron portion of the spectrometer 160 via sequential pulses appliedby the number, M, of electric field activation sources to the variouscyclotron sections D1-D4 and F2-F5 which create sequential electricfields in the cyclotron sections D1-D4 and F2-F5 at a desired frequencyor pulse rate as described hereinabove with respect to FIG. 5 to therebycause only ions supplied by the ion source that have a predefined ionmobility or range of ion mobilities defined by the frequency or pulserate to travel through the cyclotron portion of the spectrometer 160.Ions may be so directed around the cyclotron portion of the spectrometer160 any number of times, and can then be extracted from the cyclotronportion of the spectrometer 160 by controlling the ion gate G2b to blockions from passing therethrough and controlling the ion gate G2a to allowions to pass therethrough to the ion detector, DET. The number, M, ofelectric field activation sources may include two or more sources asillustrated and described hereinabove with respect to FIGS. 1-4, and theelectric fields created within the various drift tube segments D1-D4 andF2-F5 of the cyclotron portion of the spectrometer 160 by the number, M,of The electric field activation sources may be constant, linear,non-linear or have any desired shape or profile, also as describedhereinabove. Illustratively, the electric fields created in F6 and D5when extracting ions from the cyclotron portion of the spectrometer 160are constant, although these fields may alternatively also be linear,non-linear or have any desired shape or profile.

Illustratively, the memory of the control circuit has instructionsstored therein that are executable by the control circuit to control theion source voltage source, V_(IS), to produce ions, to control the iongate arrangement to direct ions around the cyclotron portion of thespectrometer 160 while blocking ions from the ion detector, and tosequentially activate the number, M, of electric field activationsources for a predefined time duration while deactivating the remainingnumber, M, of electric field activation sources to thereby cause onlyions supplied by the ion source that have a predefined ion mobility orrange of ion mobilities defined by the predefined time duration, e.g.,the activation frequency or pulse rate of the number, M, of electricfield activation sources, to travel through the cyclotron portion of thespectrometer 160 and, after the ions have traveled around the cyclotronportion of the spectrometer 160 a selected number of times, to controlthe ion gate arrangement to draw ions moving through the cyclotronportion of the spectrometer 160 into the ion exit drift tube segment andtoward the ion detector. As described hereinabove, the mobility or rangeof mobilities of ions resulting from operation of the spectrometer 160as just described is/are resonant with a fundamental frequency, f_(f),of operation of the electric field activation sources, V₁-V_(M).Alternatively or additionally, as described hereinabove with respect toFIGS. 7-9, the instructions stored in the memory of the control circuitmay include instructions that are executable by the control circuit toconduct OMS analysis, as this term has been defined hereinabove, bycontrolling the ion source voltage source, V_(IS), and the number, M, ofelectric field activation sources to sweep the activation frequency orpulse rate of the number, M, of electric field activation sources over apredefined set of activation frequencies or pulse rates to thereby causeions within the drift tube that have ion mobilities resonant with one ormore overtones, e.g., harmonic frequencies, of operation of the electricfield activation sources, V₁-V_(M), and/or that have ion mobilitiesresonant with fundamental frequencies of the activation frequencies orpulse rates, i.e., activation times, of the electric field activationsources, V₁-V_(M), for each of the discrete activation frequencies orpulse rates over the predefined set of activation frequencies or pulserates, to travel through the spectrometer 160.

Referring again to FIG. 12 a, the plot 150 represents the raffinose, R,and melezitose, M, ion peaks after 1¾ cycles of ion travel through thecyclotron portion of the instrument 160. The plot 152 similarlyrepresents the raffinose, R, and melezitose, M, ion peaks after 3¾cycles, and the plot 154 represents the raffinose, R, and melezitose, M,ion peaks after 6¾ cycles. While 1¾ cycles is sufficient to isolate eachof the raffinose and melezitose ions, it is evident from FIG. 12 a thatthe two ion peaks separate further as the number of cycles increases.

Referring now to FIG. 14, a flowchart is shown illustrating a process250 for operating the ion mobility spectrometer 160 of FIG. 12B to firstpre-fill the cyclotron portion of the spectrometer 160 with ionsgenerated by the ion source, and to then operate the spectrometer 160 asdescribed herein to cause only ions supplied by the ion source that havea predefined ion mobility or range of ion mobilities defined by theactivation frequency or pulse rate of the number, M, of electric fieldactivation sources, to travel through the spectrometer 160 and/or tosweep the activation frequency or pulse rate of the number, M, ofelectric field activation sources over a predefined set of activationfrequencies or pulse rates to thereby cause ions within the drift tubethat have ion mobilities resonant with one or more overtone, e.g.,harmonic, frequencies of operation of the electric field activationsource, V₁-V_(M), and/or that have ion mobilities resonant withfundamental frequencies of the activation frequencies or pulse rates,i.e., activation times, of the electric field activation sources,V₁-V_(M), for each of the discrete activation frequencies or pulse ratesover the predefined set of activation frequencies or pulse rates, totravel through the spectrometer 160. This process provides for asignificant increase in sensitivity and resolution compared withoperating the ion mobility spectrometer 160 with single pulses orpackets of ions produced by the ion source as described above.Illustratively, the process 250 is stored in the memory 20 of thecontrol circuit 18 in the form of instructions that are executable bythe control circuit 18 to control operation of the ion mobilityspectrometer 160. The process 250 begins at step 252 where theoperational settings of the number, M, of electric field activationsources are defined, and a value of an integer, N, is set. Inembodiments in which the spectrometer 160 will be operated to produceions having a mobility or range of mobilities that is/are resonant withonly a fundamental frequency, f_(f), of operation of the electric fieldactivation sources, V₁-V_(M), step 252 may include, for example, thesteps 82-88 of the process 80 of FIG. 5. In other embodiments in whichthe spectrometer 160 will be operated to produce ions having ionmobilities resonant with one or more overtones, e.g., harmonicfrequencies, of operation of the electric field activation sources,V₁-V_(M), step 252 may include, for example, the steps 102-106 of theprocess 100 of FIG. 7. In any case, the value of the integer, N,corresponds to the number of times ions will travel around the cyclotronportion of the drift tube defined by the ion mobility spectrometer 160.

Following step 252, the process 250 advances to step 254 where thecontrol circuit 18 is operable to control the ion source, e.g.,ESI-F1/G1, to produce ions and to open the ion gate G1, and to controlthe ion gate arrangement to open the ion gate G2b and close the iongage, G2a. By opening the ion gate G1, ions generated by the ion sourcemay thus enter the ion entrance drift tube portion of the drift tubesegment D1. By opening the ion gate G2b and closing the ion gage G2a,the generated ions will be confined to the cyclotron portion of thedrift tube (D1-D4 and F2-F5) and will be blocked from advancing to theion detector, DET, as described hereinabove. Thereafter at step 256, thecontrol circuit 18 is operable to control the electric field activationsources, V₁-V_(M), to allow ions produced by the ion source to fill thecyclotron portion of the drift tube, e.g., D1-D4 and F2-F5. In oneembodiment, step 256 comprises controlling the electric field activationsources, V₁-V_(M), in a conventional manner to allow ions of differentmobilities to enter and advance through the cyclotron portion of thedrift tube D1-D4 and F2-F5, i.e., to pass all ions generated by the ionsource from each of the plurality of drift tube segments D1-D4 and F2-F5to the next. This may be done, for example, by simultaneously andidentically activating all of the electric field activation sources,V₁-V_(M), such that a continuous, constant electric field is establishedin all of the ion transmission sections, d_(t), and ion eliminationsections, d_(e), of each of the adjacent drift tube segments. Thoseskilled in the art will recognize other techniques for controlling thevarious electric field activation sources, V₁-V₂, such that ionsgenerated by the ion source may enter and fill the cyclotron portion ofthe drift tube D1-D4 and F2-F5, and such other techniques arecontemplated by this disclosure.

Following step 256, the process 250 advances to step 258 where thecontrol circuit 18 is operable to control the ion source to stopproducing ions and to close the ion gate G1 so that no new ions from theion source enter the cyclotron portion of the drift tube. Thereafter atstep 260, the control circuit 18 is operable to set a counter, L, equalto 1, and thereafter at step 262 the control circuit 18 is operable tocontrol the electric field activation sources, V₁-V_(M), to according tosource settings, e.g., those determined at step 252, to direct ions onerevolution around the cyclotron portion of the drift tube, i.e., onecomplete path about the closed cyclotron defined by D1-D4 and F2-F5.Illustratively, the control circuit 18 is operable at step 262 tocontrol the electric field activation sources, V₁-V_(M), by sequentiallyactivating, as described hereinabove with respect to FIG. 5, one or moreof the number, M, of electric field activation sources V₁-V_(M), for thetime duration, i.e., pulse width for activation of the sources V₁-V_(M)as determined at step 252, while deactivating the remaining number, M,of electric field activation sources to thereby cause only ions withinthe drift tube (D1-D4 and F2-F5) that have a predefined ion mobility orrange of ion mobilities defined by the time duration to travel throughthe drift tube. In this embodiment, ions having the predefined ionmobility or range of ion mobilities travel, under such control at step262, one revolution around the drift tube defined by D1-D4 and F2-F5.Thereafter at step 264, the control circuit 18 is operable to determinewhether the counter, L, is equal to the number N. If not, the process250 advances to step 266 where the counter, L, is incremented by 1 andthe process 250 then loops back to again execute step 262. If, at step264, the control circuit 18 determines that L=N, then the ions havetraveled around the cyclotron portion of the drift tube (D1-D4 andF2-F5) the selected number of times, N, and the process 250 advances tostep 268.

At step 268, the control circuit 18 is operable to control the ion gatearrangement to close the ion gate G2b and open the ion gate G2a, and tocontrol the electric field activation sources, V₁-V_(M), thereafter atstep 270 to sequentially direct ions in the cyclotron portion of thedrift tube to the ion detector, DET. With the ion gate G2b closed andthe ion gate G2a open, sequential operation of the electric fieldactivation sources V₁-V_(M) in the manner just described with respect tostep 262 is thus carried out at step 270, in addition to sequentiallyactivating electric fields within F6 and D5 in like manner, tosequentially direct the ions in the cyclotron portion of the drift tubethat have the predefined ion mobilities or range of ion mobilitiesthrough the ion exit drift tube segment of D4, through F6 and D5, and tothe ion detector, DET. Optionally, the process 250 may include an extrastep 272, executed following step 270, in which the control circuit 18is operable to execute steps 254-270 until the pulse width durations,i.e., the “time durations” of activations of the electric fieldactivation sources, V₁-V_(M), have been swept through a range of pulsewidth durations between an initial pulse width duration, PW_(I) and afinal pulse width duration, PW_(F). In embodiments which include step272, step 252 will of course include a determination of PW_(I) andPW_(F) as illustrated in the process 100 of FIG. 7. Generally, PW_(I)and PW_(F) will be selected to produce one or more overtones, i.e.,harmonic frequencies of which the predefined ion mobilities or range ofion mobilities are resonant, and/or to produce ions that have ionmobilities resonant with fundamental frequencies of the activationfrequencies or pulse rates, i.e., activation times, of the electricfield activation sources, V₁-V_(M), for each of the discrete activationfrequencies or pulse rates over and between PW_(I) and PW_(F), asdescribed hereinabove.

Referring now to FIG. 15, a flowchart is shown illustrating anotherprocess 300 for operating the ion mobility spectrometer 160 of FIG. 12Bto selectively add ions from the ion source to the cyclotron portion ofthe spectrometer 160 during each of a first number of revolutions ofions around the cyclotron portion of the drift tube of the ion mobilityspectrometer 160 in which only ions that have a predefined ion mobilityor range of ion mobilities sequentially advance through the cyclotronportion of the drift tube, and to then stop adding ions and operate thespectrometer 160 as described herein to cause only ions in the cyclotronportion of the drift tube that have the predefined ion mobility or rangeof ion mobilities defined by the activation frequency or pulse rate ofthe number, M, of electric field activation sources, to travel aroundthe cyclotron portion of the drift tube a second number of times beforebeing directed to the ion detector. Optionally, this process may also bedone while also sweeping the activation frequency or pulse rate of thenumber, M, of electric field activation sources over a predefined set ofactivation frequencies or pulse rates to thereby cause ions within thedrift tube that have ion mobilities resonant with one or more overtone,e.g., harmonic, frequencies of operation of the electric fieldactivation source, V₁-V_(M), and/or to cause ions that have ionmobilities resonant with fundamental frequencies of the activationfrequencies or pulse rates, i.e., activation times, of the electricfield activation sources, V₁-V_(M), for each of a number of discreteactivation frequencies over the predefined set of activation frequenciesor pulse rates, to travel through the spectrometer 160. In any case, theprocess 300 is illustratively stored in the memory 20 of the controlcircuit 18 in the form of instructions that are executable by thecontrol circuit 18 to control operation of the ion mobility spectrometer160.

The process 300 begins at step 302 where the operational settings of thenumber, M, of electric field activation sources are defined, and valuesof two integers, N and M are set. In embodiments in which thespectrometer 160 will be operated to produce ions having a mobility orrange of mobilities that is/are resonant with only a fundamentalfrequency, f_(f), of operation of the electric field activation sourcesstep 252 may include, for example, the steps 82-88 of the process 80 ofFIG. 5. In other embodiments in which the spectrometer 160 will beoperated to produce ions having ion mobilities resonant with one or moreovertones, e.g., harmonic frequencies, of operation of the electricfield activation sources step 252 may include, for example, the steps102-106 of the process 100 of FIG. 7. In any case, the integer M set atstep 302 is different from, and should not be confused with, the number,M, of electric field activation sources.

Following step 302, the process 300 advances to step 304 where thecontrol circuit 18 is operable to control the ion source, e.g.,ESI-F1/G1, to produce ions and to control the ion gate arrangement toopen the ion gate G2b and close the ion gate, G2a. By opening the iongate G1, ions generated by the ion source may thus enter the ionentrance drift tube portion of the drift tube segment D1. By opening theion gate G2b and closing the ion gate G2a, ions introduced into thespectrometer 160 via the ion source will be confined to the cyclotronportion of the drift tube and will be blocked from advancing to the iondetector, DET, as described hereinabove. Thereafter at step 306, thecontrol circuit 18 is operable to set a counter, L, equal to 1.

Following step 306, the process 300 advances to step 308 where thecontrol circuit 18 is operable to control the ion source to open the iongate G1, and to control the electric field activation sources, V₁-V_(M),to according to source settings, e.g., those determined at step 302, toallow ions from the ion source to enter the first drift tube segment,e.g., D1, and to also advance ions already in the cyclotron portion ofthe drift tube to the next sequential drift tube segment(s). Thereafterat step 310, the control circuit 18 is operable to close the ion gateG1, and to control the electric field activation sources, V₁-V_(M),according to the source settings to advance ions in the cyclotronportion of the drift tube to the next sequential drift tube segment(s).Optionally, step 310 may also include controlling the ion source to stopproducing ions and step 308 may include controlling the ion source toproduce ions. In any case, following step 310 the process 300 advancesto step 312 where the control circuit 18 determines whether the counter,L, is equal to the sum of the integer M and another integer P. If not,the process advances to step 314 where the counter, L, is incremented by1 before again executing steps 308 and 310. If, at step 312, the controlcircuit 18 determines that L=M+P, the process 300 advances to step 316where the control circuit 18 controls the ion source to stop producingions and to reset the counter, L, equal to 1.

The sub-process of the process 300 between and including steps 302 and316 controls the ion mobility spectrometer 160 as described hereinaboveto sequentially advance only ions around the cyclotron portion of thedrift tube having ion mobilities or range of ion mobilities defined bythe activation pulse widths, i.e., time durations of activation, of theelectric field activation sources. During this process ions generated bythe ion source are also selectively added to the first drift tubesegment, D1, during and throughout a selected number, M, of revolutionsof the ions around the cyclotron portion of the drift tube (D1-D4 andF2-F5). This sub-process of the process 300 between and including steps302 and 316 may be referred to herein as “selective enhancement.” Theinteger P corresponds to the number of times steps 308 and 310 must beexecuted to sequentially fill and advance ions one revolution around thecyclotron portion of the drift tube, and the integer M corresponds tothe number of times steps 308 and 310 must be executed to continue theprocess of sequentially filling and advancing ions one revolution aroundthe cyclotron portion of the drift tube in order to direct the ionscompletely around the cyclotron portion of the drift tube a desirednumber of times while also selectively adding ions to the drift tube.The total number of revolutions, R, of the ions around the cyclotronportion of the drift tube when the “YES” branch of step 312 is satisfiedwill thus be M/P+1.

Referring now to FIGS. 16A-16L, the selective enhancement sub-process ofthe process 300 is graphically illustrated in the context of the variousdrift tube sections of the cyclotron ion mobility spectrometer 160 ofFIG. 12B. It will be understood that in FIGS. 16A-16L the ion mobilityspectrometer 160 is partitioned into eight cascaded drift tube segmentsD1-D4 and F2-F5 each having an ion transmission section, d_(t), and anion elimination region, d_(e), between the ion outlet of the iontransmission section and the ion inlet of the ion transmission sectionof the next adjacent segment. Thus, D1 has an ion elimination regionbetween the ion outlet of D1 and the ion inlet of F2, F2 has an ionelimination region between the ion outlet of F2 and the ion inlet of D2,etc. The ion elimination regions, d_(e), are not specifically shown inFIGS. 16A-16L, although it will be understood that electric fieldswithin these regions are established as described hereinabove withrespect to FIGS. 1-4 under control of the plurality of electric fieldactivation sources, V₁-V_(M). In alternative embodiments, as describedhereinabove, the drift tube segments D1-D4 may be sized to serve as theion transmission sections and the funnel segments F2-F5 may be sizedsmaller and serve as the ion elimination regions to D1-D4 respectively,or the funnel segments F2-F5 may be sized to serve as the iontransmission sections and the drift tube segments D1-D4 may be sizedsmaller and serve as the ion elimination regions to F2-F5 respectively.In any case, each sequential pair of FIGS. 16A-16L represent sequentialsnapshot of ions within the spectrometer 160 at the end of steps 308 and310 respectively. Thus, for example, FIG. 16A represents a snapshot ofions within the spectrometer 160 at the end of the first execution ofstep 308, FIG. 16B represents a snapshot of ions within the spectrometer160 at the end of the first execution of step 310, FIG. 16C represents asnapshot of ions within the spectrometer at the end of the secondexecution of step 308, etc.

Referring to FIG. 16A, the first execution of step 308 has occurred, anda group or packet of ions, I1, generated by the ion source 350 has movedthrough the ion inlet gate, G1, at the entrance of the ion entrancedrift tube segment of D1, and has moved under the influence of anelectric field established in the ion entrance drift tube segment of D1toward the ion outlet of the ion transmission segment of D1. In FIG.16B, the ion gate G1 has been closed, and the ion packet I1 has movedunder the influence of an electric field established in D1/F2 toward theion outlet of the ion transmission segment of F2.

In FIG. 16C, the ion packet I1 has moved under the influence of anelectric field established in F2/D2 toward the ion outlet of the iontransmission segment of D2. At the same time, the ion gate G1 has beenopened and another packet of ions, I2, generated by the ion source 350has moved through the ion entrance drift tube segment of D1, and hasmoved under the influence of an electric field established in the ionentrance drift tube segment of D1 toward the ion outlet of the iontransmission segment of D1. In FIG. 16D, the ion gate G1 has beenclosed, and the ion packet I1 has moved under the influence of anelectric field established in D2/F3 toward the ion outlet of the iontransmission segment of F3 and the ion packet I2 has moved under theinfluence of an electric field established in D1/F2 toward the ionoutlet of the ion transmission segment of F2.

In FIG. 16E, the ion packet I1 has moved under the influence of anelectric field established in F3/D3 toward the ion outlet of the iontransmission segment of D3, and the ion packet I2 has moved under theinfluence of an electric field established in F2/D2 toward the ionoutlet of the ion transmission segment of D2. At the same time, the iongate G1 has again been opened and another packet of ions, I3, generatedby the ion source 350 has moved through the ion entrance drift tubesegment of D1, and has moved under the influence of an electric fieldestablished in the ion entrance drift tube segment of D1 toward the ionoutlet of the ion transmission segment of D1. In FIG. 16F, the ion gateG1 has been closed, and the ion packet I1 has moved under the influenceof an electric field established in D3/F4 toward the ion outlet of theion transmission segment of F4, the ion packet I2 has moved under theinfluence of an electric field established in D2/F3 toward the ionoutlet of the ion transmission segment of F3, and the ion packet I3 hasmoved under the influence of an electric field established in D1/F2toward the ion outlet of the ion transmission segment of F2.

In FIG. 16G, the ion packet I1 has moved under the influence of anelectric field established in F4/D4 toward the ion outlet of the iontransmission segment of D4 (since G2a is closed and G2b is open), theion packet I2 has moved under the influence of an electric fieldestablished in F3/D3 toward the ion outlet of the ion transmissionsegment of D3 and the ion packet I3 has moved under the influence of anelectric field established in F2/D2 toward the ion outlet of the iontransmission segment of D2. At the same time, the ion gate G1 has againbeen opened and another packet of ions, I4, generated by the ion source350 has moved through the ion entrance drift tube segment of D1, and hasmoved under the influence of an electric field established in the ionentrance drift tube segment of D1 toward the ion outlet of the iontransmission segment of D1. In FIG. 16H, the ion gate G1 has beenclosed, and the ion packet I1 has moved under the influence of anelectric field established in D4/F5 toward the ion outlet of the iontransmission segment of F5, the ion packet I2 has moved under theinfluence of an electric field established in D3/F4 toward the ionoutlet of the ion transmission segment of F4, the ion packet I3 hasmoved under the influence of an electric field established in D2/F3toward the ion outlet of the ion transmission segment of F3 and the ionpacket I4 has moved under the influence of an electric field establishedin D1/F2 toward the ion outlet of the ion transmission segment of F2.

In FIG. 16I, the ion packet I1 has moved under the influence of anelectric field established in the cyclotron portion of F5/D1 toward theion outlet of the ion transmission segment of D1, the ion packet I2 hasmoved under the influence of an electric field established in F4/D4toward the ion outlet of the ion transmission segment of D4, the ionpacket I3 has moved under the influence of an electric field establishedin F3/D3 toward the ion outlet of the ion transmission segment of D3 andthe ion packet I4 has moved under the influence of an electric fieldestablished in F2/D2 toward the ion outlet of the ion transmissionsegment of D2. At the same time, the ion gate G1 has again been openedand another packet of ions, I5, generated by the ion source 350 hasmoved through the ion entrance drift tube segment of D1, and has movedunder the influence of an electric field established in the ion entrancedrift tube segment of D1 toward the ion outlet of the ion transmissionsegment of D1. It will be observed in FIG. 16I that as ion packets movefrom D2 to D1, the widths of the ion packets I4-I1 respectivelydecrease. This decrease in ion packet width is intended to represent afiltering of ions according to ion mobility (determined by activationpulse width of the electric field activation sources) such that fewerions are included in I1 than in I2, fewer ions are included in I2 thanin I3, etc. The ions in ion packet I1 are thus more highly resolved thanthose in I2, etc. because the illustrated ion mobility filtering processsequentially eliminates more ions having ion mobility or range of ionmobilities outside of that defined by the activation pulse width, i.e.,the time duration of activation, of the electric field activationsources, V₁-V_(M) as the ions sequentially move through the variousdrift tube segments of the cyclotron portion of the ion mobilityinstrument 160.

In FIG. 16J, the ion gate G1 has been closed, and the ion packets I1 andI5 have together moved under the influence of an electric fieldestablished in D1/F2 toward the ion outlet of the ion transmissionsegment of F2 such that ion packets I1 and I5 are now combined in F2.The ion packet I2 has also moved under the influence of an electricfield established in D4/F5 toward the ion outlet of the ion transmissionsegment of F5, the ion packet I3 has moved under the influence of anelectric field established in D3/F4 toward the ion outlet of the iontransmission segment of F4 and the ion packet I4 has moved under theinfluence of an electric field established in D2/F3 toward the ionoutlet of the ion transmission segment of F3.

In FIG. 16K, the ion packet I2 has moved under the influence of anelectric field established in the cyclotron portion of F5/D1 toward theion outlet of the ion transmission segment of D1, the ion packet I3 hasmoved under the influence of an electric field established in F4/D4toward the ion outlet of the ion transmission segment of D4, the ionpacket I4 has moved under the influence of an electric field establishedin F3/D3 toward the ion outlet of the ion transmission segment of D3 andthe combination of ion packets I1 and I5 have moved under the influenceof an electric field established in F2/D2 toward the ion outlet of theion transmission segment of D2. At the same time, the ion gate G1 hasagain been opened and another packet of ions, I6, generated by the ionsource 350 has moved through the ion entrance drift tube segment of D1,and has moved under the influence of an electric field established inthe ion entrance drift tube segment of D1 toward the ion outlet of theion transmission segment of D1. In FIG. 16L, the ion gate G1 has beenclosed, and the ion packets I2 and 16 have together moved under theinfluence of an electric field established in D1/F2 toward the ionoutlet of the ion transmission segment of F2 such that ion packets I2and 16 are now combined in F2. The ion packet I3 has also moved underthe influence of an electric field established in D4/F5 toward the ionoutlet of the ion transmission segment of F5, the ion packet I4 hasmoved under the influence of an electric field established in D3/F4toward the ion outlet of the ion transmission segment of F4 and thecombination of ion packets I1 and I5 has moved under the influence of anelectric field established in D2/F3 toward the ion outlet of the iontransmission segment of F3.

Referring again to FIG. 15, the sub-process carried out by steps 302-316of the process 300 and illustrated in FIGS. 16A-16L can be executed anynumber of times to selectively add ions to individual packets of ionscirculating through the various drift tube segments D1-D4 and F2-F5 ofthe ion mobility spectrometer 160. As illustrated in FIGS. 16A-16H, theloop defined by steps 308-314 is executed four times to complete onerevolution of ions around the cyclotron portion (D1-D4 and F2-F5) of theion mobility spectrometer 160. Thus, “P” at step 312 is equal to four inthe illustrated embodiment, and the counter value “M” is thereforeselected such that the total desired number of revolutions, R, of ionsaround the cyclotron portion of the ion mobility spectrometer 160 duringthe selective enhancement sub-process of steps 302-316, i.e., duringwhich ions from the ion source 350 are selectively added to ions alreadycirculating through the cyclotron portion of the spectrometer 160, mustsatisfy the relation R=M/P+1 as described above.

It will be understood that the ion mobility spectrometer 160 may becontrolled and operated using similar yet alternate techniques toperform the selective enhancement process just illustrated and describedwith respect to FIGS. 16A-16L. For example, the spectrometer 160 may bealternatively operated such that ions from the ion source 350 fill theD1 and F2 regions during one field application setting. Next the fieldswould switch such that ions from F2 would move into the D2 region whileions from the source 350 would be shut off. Application of the nextfield would see the transmission of the ions with resonant mobilitiesinto the F3 region. At the same time, ions from the ion source 350 wouldbe allowed to fill the D1 and F2 regions again. Completion of anothertwo field application periods would yield ions in the F4 and F3 regionswith a filling of the D1 and F2 regions. Yet another two applicationperiods would result in ions in the F5, F4, and F3 regions as well as afilling of the D1 and F2 regions. With the addition of two moreapplication periods the first ion packet would reach the F2 region againhaving completed a full cycle around the cyclotron portion of the drifttube (D1-D4 and F2-F5). During this time, ions from the source would beallowed into the D1 and F2 region combining with this ion packet.Another cycle would see the filtering of these added ions according toresonant mobilities. Ions could be added to each successive packet for adesired amount of time or a desired number of cycles around thecyclotron portion of the drift tube (D1-D4 and F2-F5). Alternativelystill, the process just described could be modified to move ions aroundthe cyclotron portion of the spectrometer 160 using longer iontransmission regions. For example, the spectrometer 160 may bealternatively operated such that ions from the ion source 350 fill theD1 and F2 regions during one field application setting. The ion sourcemay then be shut off and an electric field may be activated in theD1/F2/D2/F3 region to move ions into the D2/F3 region, etc. Ions maythus be moved through the cyclotron portion of the spectrometer 160 bypropagating two regions worth of ions around the cyclotron portion usingfewer field applications to complete each traversal of the cyclotronportion of the spectrometer 160.

As described hereinabove, the design of the cyclotron portion of thedrift can be altered from that described above such that the D regionscomprise the ion transmission regions, d_(t), and the F regions comprisethe ion elimination regions, d_(e), or such that the F regions comprisethe ion transmission regions, d_(t), and the D regions comprise the ionelimination regions, d_(e). Those skilled in the art will recognize thatthe selective enhancement sub-process just described comprising steps302-316 may be easily modified to be performed using such an alternatedesign of the cyclotron portion of the drift tube (D1-D4 and F2-F5), andthat any such modifications to steps 302-316 would be a mere mechanicalstep for a skilled artisan.

Referring again to FIG. 15, the process 300 advances from step 316 tosteps 318-326, and optional also to step 328. Steps 318-328 areidentical to steps 262-272 illustrated and described hereinabove withrespect to FIG. 14, in which the control circuit 18 is operable tocontrol the electric field activation sources, V₁-V_(M), and the iongates G2a and G2b to cause the ions within the cyclotron portion of theion mobility spectrometer 160 to travel around the cyclotron drift tube“N” times prior to directing the ions to the ion detector, DET, where Nmay be any positive integer. Optionally, step 328 may be included toperform overtone analysis, as this process is described above, using thecombination of the selective enhancement sub-process described abovefollowed by controlling the spectrometer 160 to circulate thepost-selectively enhanced ions in the cyclotron drift tube N times priorto directing the ions toward the ion detector, DET.

Mixtures may alternatively be resolved over long distances in lineardrift tubes, e.g., of the type illustrated in FIGS. 1-4, at or neartheir fundamental frequencies by controlling the electric fieldactivation sources, V₁-V_(M), in a manner that directs ions back andforth between the ends of the drift tube. More specifically, ionsentering the ion inlet of the drift tube 14 are directed by the electricfield activation sources, V₁-V_(M), toward the ion outlet of the drifttube 14 by selectively controlling the activation times and pulse widthsof the electric field activation sources as described hereinabove withrespect to FIGS. 1-5. In this embodiment, prior to reaching the ionoutlet, e.g., at or near the last drift tube segment, the controlcircuit 18 may control the electric field activation sources, V₁-V_(M),to reverse the direction of the sequentially applied electric fields tothe cascaded drift tube segments such that the ions reverse directionand move linearly toward the ion inlet of the drift tube 14. As before,the duration of the pulse widths, PW, would determine the range of ionmobilities of the ions traversing the drift tube 14. In any case, thismay be repeated any number of times to allow the ions to drift anydesired distance. After drifting the desired distance, a gate at the ionoutlet of the drift tube 14 may be activated to allow the ions to exitthe ion outlet of the drift tube 14 and be detected by an ion detectorpositioned to detect ions exiting the drift tube.

Running the drift separation in a back and forth manner as justdescribed can be limited in that ions that limit resolving power, e.g.,those with slightly mismatched mobilities, may not eliminated as theymove back to their initial positions on all even passes (i.e., the2^(nd), 4^(th), 6^(th) etc. pass through the drift tube). Thislimitation may be overcome by, for example, randomizing positions of theions in the drift tube during each pass of ions from the first drifttube segment to the last and/or during each pass of ions from the lastdrift tube segment to the first.

Referring now to FIG. 17, one illustrative embodiment of an ion mobilityspectrometer 400 is shown having a linear drift tube 14′ that isconfigured to randomize ion positions during each such pass of ions. Thedrift tube 14′ is identical to the drift tube 14 illustrated anddescribed hereinabove with respect to FIGS. 1-4 except that aconventional ion trap 402 is positioned between two adjacent ones of thenumber, N, of cascaded drift tube segments, e.g., between the ion outletof the third ion elimination region, d_(e)(3) and the ion inlet of thefourth ion transmission region, d_(t)(4). All other features of thedrift tube 14′ are identical to the drift tube 14 illustrated anddescribed hereinabove, and all other components of the ion mobilityspectrometer 400 are identical to correspondingly numbered components ofthe ion mobility spectrometer 10 illustrated and described hereinabove.The primary purpose of the ion trap 402 in the spectrometer 400 is totrap ions of the desired mobility during each pass of ions from thefirst drift tube segment to the last and/or during each pass of ionsfrom the last drift tube segment to the first to thereby randomize thepositions of the ions during each such pass. In this regard, the memory20 of the processor 18 has, in this embodiment, instructions storedtherein that are executable by the processor 18 to control the ion trap,e.g., via a suitable voltage source or voltage sources, which may or maynot be, or be part of, one or more of the electric field activationsources, V₁-V_(M), to trap ions therein during each pass of ions fromthe first drift tube segment to the last and/or during each pass of ionsfrom the last drift tube segment to the first for a trap period selectedto allow ions trapped within the ion trap 402 to randomize theirpositions relative to the ion trap 402 and thereby randomize theirpositions relative to the drift tube 14′. During the trap period, ionswill thus randomize their positions, causing a greater mismatch intiming for a population of undesired ions, e.g., those with slightlyoff-resonance mobilities. This will lead to more effective eliminationof these undesired ions. It will be understood that the ion trap 402illustrated in FIG. 17 may be alternatively positioned anywhere alongits length, i.e., at either end or between any two adjacent drift tubesegments. Alternatively or additionally, the drift tube 14′ may includetwo or more such ion traps 402 positioned anywhere along its length. Inone specific embodiment, for example, one such ion trap 402 ispositioned at one end of the drift tube 14′ and another such ion trap402 is positioned at an opposite end of the drift tube 14′. In thisembodiment, the control circuit controls each ion trap to trap ionstherein during each pass of ions from one end of the drift tube tot theother.

Referring now to FIG. 18, the ion mobility spectrometer 10 of FIG. 1 isshown alternatively configured to randomize ion positions during eachsuch pass of ions. In particular, the instructions stored in the memory20 include, in the embodiment illustrated in FIG. 18, instructions thatare executable by the control circuit 18 to control the strengths, i.e.,i.e., the magnitudes, of the electric fields established by the electricfield activation sources, V₁-V_(M), in a number of adjacent drift tubesegments. More specifically, the electric fields in a number of adjacentdrift tube segments are progressively diminished to cause the ions torandomize their positions relative to the drift tube 14 by bunching upin one or more of the number of adjacent drift tube segments. In theembodiment illustrated in FIG. 18, for example, the control circuit 18is configured to control the electric field activation sources,V₁-V_(M), to cause the magnitudes of the electric fields E₁-E₄ in thefour adjacent drift tube segments at each end of the drift tube todiminish such that E₁>E₂>E₃>E₄. In alternative embodiments, the numberof adjacent drift tube segments in which the electric fields arediminished in magnitude may be more or fewer, may comprise any number ofsuch adjacent drift tube segments at either or both ends of the drifttube 14, or may comprise any number of such adjacent drift tube segmentsbetween the two ends of the drift tube 14.

The back-and-forth mobility separation in the segmented drift tube asjust describe with respect to FIGS. 17 and 18 may alternatively oradditionally be used for OMS modes of operation as described hereinabovewith respect to FIG. 7. This allows the use of overtone frequencies as ameans of mobility selection. Additionally, such a device couldincorporate ion trapping on either end to allow for selective enrichmentof a mobility region prior to mobility selection refinement with theback-and-forth cycling of ions. Here, ions from a continuous or pulsedsource can pass through a linear drift tube in either direction andthose with resonant frequencies can be trapped in an ion trap positionedin the drift tube. After selective filling for a predetermined timeperiod, i.e., as described hereinabove with respect to FIGS. 16A-16L,the ions would then be cycled back-and-forth through the linear drifttube a number of times to obtain greater resolution (isolation of ionsof a given mobility). Referring to FIG. 19, one illustrative embodimentof such an ion mobility spectrometer 500 is shown in which an ion trap502 is positioned at the end of the linear drift tube 14″, which isotherwise identical to the drift tube 14 of FIGS. 1-4. The remainingcomponents of the spectrometer 500 are likewise identical tolike-numbered components of the spectrometer 10 of FIGS. 1-4 except thatthe memory includes instructions stored therein that are executable bythe control circuit 18 to control and operate the spectrometer 500 toselectively fill the drift tube 14″ for a predefined time period ornumber of back and forth cycles, and to thereafter cycle the ions backand forth a desired number of times as generally described hereinabovewith respect to FIGS. 15-16L.

Referring now to FIG. 20, a flowchart is shown of one illustrativeembodiment of a process 600 for operating the linear drift tube 14″ ofFIG. 19 as just described. Illustratively, the process 600 is stored inthe memory 20 of the control circuit 18 in the form of instructions thatare executable by the processor 18 to control operation of thespectrometer 500. The process 600 begins at step 602 where theoperational settings of the number, M, of electric field activationsources are defined, and a value of an integer, N, (and optionally M) isset. In embodiments in which the spectrometer 500 will be operated toproduce ions having a mobility or range of mobilities that is/areresonant with only a fundamental frequency, f_(f), of operation of theelectric field activation sources, V₁-V_(M), step 602 may include, forexample, the steps 82-88 of the process 80 of FIG. 5. In otherembodiments in which the spectrometer 500 will be operated to produceions having ion mobilities resonant with one or more overtones, e.g.,harmonic frequencies, of operation of the electric field activationsources, V₁-V_(M), step 602 may include, for example, the steps 102-106of the process 100 of FIG. 7.

Following step 602, the process 600 advances to step 604 where thecontrol circuit 18 is operable in one embodiment to reset a timer, e.g.,set a timer value, T, to zero (or to another arbitrary value), and in analternate embodiment to set a counter value, K, equal to 1. Thereafterat step 606, the control circuit 18 is operable to control the ionsource 12 to generate ions, and thereafter at step 608 the controlcircuit 18 is operable to control the electric field activation sources,V₁-V_(M), according to the source settings determined at step 602 tosequentially advance ions sequentially through the drift tube segmentstoward the last drift tube segment, i.e., toward the ion trap 502. Theions advance through the drift tube at step 608 will, of course, haveion mobilities or ranges of ion mobilities that are resonant with theactivation time, i.e., time duration of activation, of the electricfield activation sources V₁-V_(M) as illustrated and describedhereinabove. Thereafter at step 610, the control circuit 18 is operableto control the ion trap 502 to trap ions advanced through the drift tube14″ to the ion trap 502. Thereafter at step 612, the control circuit 18is operable to determine whether the timer has reached a predefined timeperiod, T_(P), since being reset, or to determine whether the value ofthe counter, K, has reached the value M which was optionally set at step602. In some embodiments, the ion source 12 is controlled at step 606 tocontinuously generate ions, and in other embodiments the ion source 12is controlled at step 606 to generate discrete packets or pulses ofions. In either case, a timer or a counter may be used to control theamount of time that ions are collected in the ion trap 502 or the numberof passes in which ions are advanced into the ion trap via the drifttube 14″. If a timer is used, step 612 loops back to step 606 (or tostep 608 in the case of continuous generation of ions) until T>T_(P). Ifa counter is used, step 612 advances to step 614 to increment K, and tothen loop back to step 606 (or to step 608 in the case of continuousgeneration of ions) until K=M, where M=the number of times ions areadvanced through the drift tube 14″ into the ion trap 502. In eithercase, the “YES” branch of step 612 advances to step 616 where thecontrol circuit 18 is operable to stop producing ions and to set acounter value, L, equal to 1.

Following step 616, the process 600 advances to step 618 where thecontrol circuit 18 controls the ion trap 502 and the electric fieldactivation sources, V₁-V_(M), to according to source settings, e.g.,those determined at step 602, to sequentially advance ions in the iontrap 502 in a reverse direction toward the first drift segment of thedrift tube 14″, i.e., to the d_(t)(1). When the ions are determined atstep 620 by the control circuit 18 to be in the first drift tube segment(e.g., as a function of time after being released from the ion trap 502at step 618), the process advances to step 622, and otherwise loops backto step 618 until step 620 is satisfied. At step 622, the controlcircuit 18 controls the electric field activation sources, V₁-V_(M), toaccording to source settings, e.g., those determined at step 602, tosequentially advance ions in the ion trap 502 in a forward directionfrom the first drift tube segment, d_(t)(1) toward last drift tubesegment, i.e., the ion trap 502. Thereafter at step 624, the controlcircuit 18 is operable to control the ion trap 502 to trap therein ionspassing through the last drift tube segment for a time period, T_(T),where T_(T) is a trapping time period that allows the ions to randomizeas described hereinabove with respect to FIG. 17. Thereafter at step626, the control circuit 18 is operable to determine whether thecounter, L, is equal to the number N. If not, the process 600 advancesto step 628 where the counter, L, is incremented by 1 and the process600 then loops back to again execute step 618. If, at step 626, thecontrol circuit 18 determines that L=N, then the ions have traversed thelinear drift tube 14″ the desired number of times, and the process 600advances to step 630 where the control circuit 18 is operable to controlthe ion trap 502 to direct ions trapped therein to the ion detector 16.Optionally, the process 600 may include an extra step 632, executedfollowing step 630, in which the control circuit 18 is operable toexecute steps 604-630 until the pulse width durations, i.e., the “timedurations” of activations of the electric field activation sources,V₁-V_(M), have been swept through a range of pulse width durationsbetween an initial pulse width duration, PW_(I) and a final pulse widthduration, PW_(F). In embodiments which include step 632, step 602 willof course include a determination of PW_(I) and PW_(F) as illustrated inthe process 100 of FIG. 7. Generally, PW_(I) and PW_(F) will be selectedto produce one or more overtones, i.e., harmonic frequencies of whichthe predefined ion mobilities or range of ion mobilities are resonant,and/or to produce ions that have ion mobilities resonant withfundamental frequencies of the activation frequencies or pulse rates,i.e., activation times, of the electric field activation sources,V₁-V_(M), for each of the discrete activation frequencies or pulse ratesover and between PW_(I) and PW_(F), as described hereinabove.

While the spectrometer 500 illustrated in FIG. 19 is illustrated withthe ion trap 502 located at one end of the drift tube 14″, it will beunderstood that the ion trap 502 may alternatively be positioned at theopposite end of the drift tube 14″ or between the two ends of the drifttube 14″. Alternatively or additionally, any number of ion traps may bepositioned in the drift tube 14″, e.g., one at each end, for the purposeof trapping and randomizing positions of the ions trapped therein asillustrated and described with respect to FIG. 17, and/or the magnitudesof the electric fields of a number of adjacent ones of the drift tubesegments may be sequentially diminished to enhance or achieve thisresult as illustrated and described with respect to FIG. 18. In suchcase or cases, the ion trap 502 may, need not, be controlled in asdescribed for the purpose of randomizing ions trapped therein.

In any of the linear or cyclotron configurations of the ion mobilityspectrometer illustrated and described herein, a non-destructivedetector, e.g., rather than an ion counting detector 16, could be usedthat is configured to measure the image charge many times at a specifiedposition within drift tube. Ion distributions could then be recorded asthe frequency that ions pass the non-destructive detector. Aconventional frequency transformation, e.g., Fourier transform, couldthen be used to back-calculate ion mobility.

Referring now to FIG. 21, yet another embodiment of an ion mobilityspectrometer 600 is shown. In the illustrated embodiment, some of theillustrated components are identical to those described hereinabove, andlike reference numbers are therefore used to identify like components.In FIG. 21, the drift tube 602 includes a single drift tube segment oflength L positioned between two ion traps 604 and 606. The ion trap 604is positioned adjacent to the inlet of the single drift tube segment602, and the ion trap 606 is positioned adjacent to the ion outlet ofthe single drift tube segment 602. At least one drift tube voltagesource, V_(DT), is electrically connected between the control circuit 18and the single drift tube segment 602, and is controllable in aconventional manner to establish an electric field in the single drifttube region 602 in one direction that causes ions supplied by the ionsource 12 to drift from the ion trap 604 toward the ion trap 606, and toalternatively establish an electric drift field in the single drift tuberegion 602 in an opposite direction that causes ions to drift from theion trap 606 toward the ion trap 604. An ion trap voltage source,V_(IT1), is electrically connected between the control circuit 18 andthe ion trap 604, and another ion trap voltage source, V_(IT2), iselectrically connected between the control circuit 18 and the ion trap606.

The memory 20 illustratively includes instructions stored therein thatare executable by the control circuit 18 to execute a process apredefined number of times. The process illustratively includesactivating the at least one electric field activation source, V_(DT),for a time duration to establish an electric field in the one directionto cause only ions supplied by the ion source 12 that have a predefinedion mobility or range of ion mobilities defined by the time duration totravel through the single drift tube region 602 in the direction fromthe ion trap 604 toward the second ion trap 606 followed by controllingthe ion trap 606 to trap therein the ions that have the predefined ionmobility or range of ion mobilities. The ion trap 606 is then controlledto release the ions trapped therein and the control circuit 18 thenactivates the at least one electric field activation source, V_(DT), forthe time duration to establish an electric field in the oppositedirection to cause only ions that have the predefined ion mobility orrange of ion mobilities defined by the time duration to travel throughthe single drift tube region 602 in the direction from the ion trap 606toward the ion trap 604 followed by controlling the ion trap 604 to traptherein the ions that have the predefined ion mobility or range of ionmobilities followed by controlling the ion trap 604 to release the ionstrapped therein. This process may be performed any number of times tothereby cause ions to traverse the single drift tube region 602 any suchnumber of times. The control circuit 18 may then control the ion trap606 to release ions trapped therein toward the ion detector 16 and toprocess the ion detection signals produced by the ion detector todetermine ion mobility spectral information therefrom. The ion source 12may be controlled in a pulsed fashion to produce discrete packets ofions or may alternatively be controlled to continuously produce ions.The instructions stored in the memory 20 may further includeinstructions executable by the control circuit 18 to control the iontraps 604 and 606 to trap ions therein for a trap period. The trapperiod is illustratively selected to allow ions trapped within the iontrap 604 and within the ion trap 606 to randomize their positionsrelative to the respective ion trap 604/606.

The spectrometer 600 may alternatively be operated in the OMS modeillustrated and described hereinabove. For example, the instructionsstored in the memory 20 may further include instructions executable bythe control circuit 18 to control the at least one electric fieldactivation source, V_(DT), to sweep the time duration between first andsecond predefined time durations to thereby cause ions that havefundamental frequencies resonant with each of a number of discrete timedurations between the first and second time durations to travel throughthe single drift tube region 602, and to execute the process thepredefined number of times for each of the number of discrete timedurations between the first and second predefined time durations.

Referring now to FIG. 13, a block diagram of one illustrative embodimentof a cascaded ion mobility spectrometer instrument 170 is shown thatemploys some of the concepts illustrated and described hereinabove withrespect to FIGS. 1-12B. In the illustrated embodiment, the instrument170 includes an ion source 12 having an ion outlet coupled to an ioninlet of a first ion mobility spectrometer (IMS1). An ion outlet of IMS1is coupled to an ion inlet of a second ion mobility spectrometer (IMS2)having an ion outlet that is coupled to an ion detector 16. The IMS1 hasan axial length of L1 and the IMS2 has an axial length of L2. A controlcircuit 180 includes a memory unit 182, and is electrically connected toa control input of an ion source voltage supply, V_(IS), having anoutput that is electrically connected to the ion source 12. Theinstrument 170 further includes a plurality of electric field activationsources, V₁-V_(Q), that are electrically connected between the controlcircuit 180 and IMS1 and IMS2, where Q may be any integer greaterthan 1. Illustratively, a subset of the electric field activationsources, V₁-V_(P), are dedicated to IMS1, and another subset,V_(P+1)-V_(Q) are dedicated to IMS2. Alternatively, V_(P+1)-V_(Q) may beomitted, and V₁-V_(P) may be used for both of IMS1 and IMS2. In anycase, each of the foregoing components may be as described hereinabovewith respect to the embodiment of FIG. 1. In one illustrativeembodiment, the instrument 170 is operable just as described hereinabovewith respect to any of FIGS. 1-12B, except that the ions are resolvedover an effective drift tube length of L1+L2 rather than over the lengthof a single drift tube, such that IMS1 and IMS2 together form a singleion mobility spectrometer.

The ion mobility spectrometer instrument 170 of FIG. 13 may furtherinclude at least one additional voltage source, V_(F), which may becontrolled by the control circuit 180 to produce one or more voltagesthat control one or more ion fragmentation units or other conventionaldevice for inducing structural changes in ions within IMS1, IMS2 and/orpositioned between IMS1 and IMS2. In embodiments in which the drifttubes of IMS1 and IMS2 are constructed according to the teachings ofco-pending U.S. Patent Application Pub. No. US 2007/0114382, forexample, an ion activation region of the type described therein may bepositioned at the end of any one or more ion funnels that form IMS1and/or IMS2. Alternatively, IMS1 and/or IMS2 may be modified in otherembodiments to include one or more conventional structural changeinducing devices or stages, e.g., one or more ion fragmentation stages,ion conformational change stages, and/or other conventional structuralchange inducing devices or stages, therein or interposed between IMS1and IMS2. For example, such a structural change inducing device may bepositioned between IMS1 and IMS2, and the ion mobility spectrometer 170may be operated as described hereinabove to conduct fundamentalfrequency and/or overtone frequency analysis with IMS1, to then inducestructural changes in ions emerging from IMS1, and to then conductfundamental frequency and/or overtone frequency analysis with IMS2 onthe ions in which structural changes were induced. Alternatively oradditionally, the fragmented ions may be mobility filtered in aconventional manner prior to entering IMS2. Alternatively oradditionally still, such fragmented and mobility-selected ions may befurther fragmented and possibly further mobility selected any number oftimes prior to entrance into IMS2.

IMS1 may further include an operating condition selection unit 190, andIMS2 may likewise include an operating condition selection unit 200. Theoperating condition selection units 190 and 200 may be manuallycontrolled via respective manual controls 194 and 204, and/or may beautomatically controlled by the control circuit 180 via suitableelectrical control lines 192 and 202 respectively. The operatingcondition selection units 190 and 200 are block diagram components thatmay represent conventional structures that control any one or more ofthe operating temperature of IMS1 and/or IMS2, the operating pressure ofIMS1 and/or IMS2, the chemical make up and/or flow rate of gas, e.g.,buffer gas, supplied to the ion pathway of IMS1 and/or IMS2, and thelike. In the operation of the ion mobility spectrometer instrument 170,such as described hereinabove, IMS1 and IMS2 may be operated asdescribed hereinabove and further with any one or more of, or with anycombination of, the same or different drift tube lengths, L1 and L2, thesame or different electrical field strengths applied by the electricfield activation sources V₁-V_(Q), the same or different pulse shapesapplied by the electric field activation sources V₁-V_(Q), the same ordifferent pulse width durations, PW, applied by the electric fieldactivation sources V₁-V_(Q), the same or different operatingtemperatures (e.g., T1 for IMS1 and T2 for IMS2), the same or differentoperating pressures, (e.g., P1 for IMS1 and P2 for IMS2), with the ionspassing through IMS1 and IMS2 exposed to the same or different gasses(Gas1 for IMS1 and Gas2 for IMS2), or with ion fragmentation occurringwithin or between IMS1 and IMS2. Further details relating to some ofthese operational scenarios or modes are provided in U.S. Pat. No.7,077,904, the disclosure of which is incorporated herein by reference.

It will be understood that the ion mobility spectrometer instrumentillustrated in FIG. 13 and described herein represents only an examplemultiple drift tube instrument, and that the instrument mayalternatively include any number of IMS units or drift tubes.Alternatively still, the IMS drift tubes in such an arrangement need notbe linear, and the instrument 170 illustrated in FIG. 13 may include anynumber of non-linear IMS drift tube, such as two or more circular drifttubes of the type described in co-pending PCT Publication No. WO2008/028159 A2, filed Aug. 1, 2007, the disclosure of which has beenincorporated herein by reference.

Transmission of ions through the various drift tube segments S₁-S_(N) ofany of the ion mobility spectrometer instruments described above, bysequentially activating the electric field activation sources V₁-V_(M),is possible only if the mobilities of the ions are in resonance with theswitching rates of the electric fields applied by these electric fieldactivation sources. This is true regardless of the phase, φ, of thespectrometer, which refers to the number of electric field activationsources, arranged and connected to the various drift tube segments andion elimination regions as described above (see e.g., FIGS. 4A-4D).Thus, to transmit ions sequentially through the various drift tubesegments S₁-S_(N) as just described, the ions must have mobilities thatallow traversal of exactly one drift tube segment in one fieldapplication duration. Ions with mobilities that are off resonance eithertraversing a drift tube segment too quickly or too slowly are eventuallyeliminated in one of the ion elimination regions d_(e). In the operationof any of the ion mobility spectrometers illustrated and describedabove, the switching rates of each of the electric field activationsources, V₁-V_(M), have been equal, and the frequency at which thevarious electric field activation sources are switched on/off, i.e., thefrequency at which the ions have resonant mobilities, is termed thefundamental frequency, f_(f).

As also described in detail above, such operation of the electric fieldactivation sources V₁-V_(M) has led to a technique referred to asOvertone Mobility Spectrometry (OMS) because of its ability toselectively transmit ions in different frequency regions, includingthose associated with higher overtones. And for any given phase, φ, suchovertones in embodiments of the ion mobility spectrometer illustratedand described herein that are operated with uniform, constant electricfields in the various drift tube segments, S₁-S_(N), are predictablygiven by the equation H=φ(h−1)+1, h=1, 2, 3, . . . , where H is aharmonic number, φ is the phase of the ion mobility spectrometer 10, andh is an integer index. Thus, it was demonstrated above that for a2-phase, system, H=1, 3, 5, 7, . . . , for a 3-phase system, H=1, 4, 7,10, . . . , for a 4-phase system, H=1, 5, 9, 13, . . . , etc.

However, whereas resolving power increases with increasing overtone,overlap of ions from flanking frequency regions tends to limit theoverall peak capacity with higher overtones. This limitation can beovercome with an attendant increase in peak capacity by modifying theOMS techniques described above to cause at least one of the electricfield activation sources to have a different activation time durationthan activation time durations of others of the electric fieldactivation sources. As will be described in detail below, this techniquecan be used to select sub-species of OMS peaks, i.e., selectedovertones, while filtering out others, and may therefore be referred toas Selected Overtone Mobility Spectrometry (SOMS). As will also bedescribed in detail below, SOMS can also be used to select and observepreviously unobserved integer overtones as well as non-integerovertones. These concepts will be introduced below with reference to2-phase arrangements (φ=2) of the type illustrated and described above,and will then be extended or generalized to systems with φ>2. It shouldbe understood, however, that the various SOMS concepts and techniquedescribed below may be implemented with any of the various ion mobilityspectrometer configurations illustrated and described above, includingany and all linear and/or circular drift tube arrangements.

Referring now to FIG. 22A, a timing diagram 40 is shown illustrating aseries of drift tube segments, d_(t)(1), d_(t)(2), . . . , operated witha two-phase arrangement of electric field activation sources havingequal activation durations selected to define the 3^(rd) overtone of thefundamental frequency of operation as described above with respect toOMS operation. The activation durations of the electric field activationsource V₁ is designated by the letter “A” in FIG. 22A, and correspondsto the shaded squares. The activation durations of the electric fieldactivation source V₂, on the other hand, is designated by the letter “B”in FIG. 22A, and corresponds to the white squares. If the time spanacross one drift tube segment, e.g., d_(t)(1) is defined as 1/f_(f),then only ions having mobilities resonant with f_(f) will be transmittedfrom one drift tube segment to the next. Such ions will also betransmitted at higher overtones of f_(f), and in a 2-phase system onesuch overtone is the third overtone, or 3f_(f). It is this operationthat is illustrated in FIG. 22A, and it can thus be observed that 3transitions (e.g., 3f_(f)) between V₁ and V₂ occur in each drift tubesegment to illustrate movement of a packet of ions along the drift tubein the 3^(rd) overtone. Likewise, a total of 6 equal-durationtransitions between V₁ and V₂ occur between each set of two drift tubesegments, e.g., d_(t)(1) and d_(t)(2), as the packet of ions move alongthe drift tube in the 3^(rd) overtone as indicated by reference number700 in FIG. 22A.

Referring now to FIG. 22B, a timing diagram 40′ similar to FIG. 22A isshown and illustrates the two-phase arrangement of electric fieldactivation sources having unequal activation durations in each phase,but which are also selected to define the 3^(rd) overtone of thefundamental frequency of operation. Between each set of two drift tubesegments, e.g., .g., d_(t)(1) and d_(t)(2), V₁ is activated for only asingle shaded square whereas V₂ is activated for the next consecutive 5white squares as indicated by reference number 702 in FIG. 22B. A phaseratio, ζ, is defined as the ratio of the activation duration of anarbitrary one of the electric field activation sources, e.g., V₂, andthe activation duration of the other electric field activation source,e.g., V₁. In the example illustrated in FIG. 22B, the phase ratio, ζ, isthus 5/1, or 5, and in the 2-phase system the 3^(rd) overtone is thusdefined for ζ=5. It can be similarly shown (although not shown in thefigures) that in the 2-phase system the 5^(th) overtone is defined forζ=9. This then leads to the generalized result m_(eq)=(ζ+1)/2, wherem_(eq) is the equivalent overtone number for a given phase ratio, andthe frequency, f_(eq), at which the equivalent overtone occurs, relativeto the fundamental frequency, f_(f), of the OMS system, is given by therelationship f_(eq)=M_(eq)f_(f).

In OMS, there is a maximum overtone at which the distance traveled by apacket of ions in a single phase is shorter than the length of an ionelimination region, e.g., d_(e)(1). As discussed above, an ion packetwill be filtered out if it is within an ion elimination region when arepulsive electric field is established within that region, and themaximum overtone is thus given by the relationshipm_(max)=(I_(t)+I_(e))/I_(e), where I_(t) is the length of each of thedrift tube segments d_(t)(1), d_(t)(2), . . . , and I_(e) is the lengthof the ion elimination regions, d_(e)(1), d_(e)(2), . . . .

The same maximum overtone limitation holds true for SOMS, and combiningthe above equations for m_(eq) and m_(max) yields the following equationfor the maximum phase ratio, ζ_(max)=[2(I_(t)+I_(e))/I_(e)]−1.

As can be seen in FIG. 22B, the duty cycle of the fundamental peak inSOMS is less than that of the equivalent OMS for an overtone greaterthan one, due to the lack of repeats of the packets within the two drifttube segment distance. This results in a multiplicative loss in dutycycle equivalent to the overtone, which is given by the relationshipDuty Cycle=[(I_(t)+I_(e))−I_(e)]/2m(I_(t)+I_(e)).

The fundamental peak of a SOMS system is the peak at the lowestfrequency, and is analogous but not equivalent to the peak at thefundamental frequency in an OMS system. This is because the fundamentalpeak in a SOMS system is, by definition, an overtone in the OMS system.And just as a 2-phase OMS system has 3^(rd), 5^(th), 7^(th), etc.overtones, so too does a 2-phase SOMS system, wherein each such overtonein the SOMS system has an equivalent overtone, m_(eq) defined by thephase ratio. For example, referring to FIG. 23A, the fundamental peakand the 3^(rd), 5^(th) and 7^(th) overtones are shown for an examplesimulated spectrum 710 of a SOMS system in which the phase ratio, ζ,is 1. With a phase ratio, ζ, of 1, the SOMS system reduces to the OMSsystem illustrated and described above, and fundamental peak, as well asthe equivalent overtones, m_(eq), are thus identical to the fundamentalpeak and overtone values of the OMS system, i.e., m=1, m=3, m=5 and m=7.However, as illustrated in FIG. 23B, in a SOMS system having a phaseratio, ζ, of 5, the above equation for the equivalent overtone m_(eq)reveals that the fundamental peak for this SOMS system is equivalent tothe 3^(rd) overtone in the OMS system. SOMS can thus be used to selectovertones for observation while also filtering out other overtones.

Referring now to FIG. 24, a flowchart is shown of an embodiment of aprocess 750 for selecting an overtone to transmit through an ionmobility spectrometer using the SOMS technique just described. Theprocess 750 illustrated in FIG. 24 may be provided, in whole or in part,in the form of instructions that are stored in the memory unit 20 of thecontrol circuit 18 and that are executable by the control circuit 18 tocontrol any implementation of an ion mobility spectrometer instrumentillustrated and described herein, in accordance with the process 750. Inany case, the process 750 begins at step 752 where the frequency orfrequency range, FR, at which the selected overtone occurs is selected.Generally, the frequency or frequency range sought at step 752 is thefrequency, f_(eq), at which the equivalent overtone occurs relative tothe fundamental frequency, f_(f), of the OMS system, and is given by therelationship f_(eq)=m_(eq)f_(f). Thus, if the fundamental frequency,f_(f), is known, then the frequency, f_(eq), at which any selectedovertone, m_(eq), occurs is given by this relationship.

The process 750 advances from step 752 to step 754 where the phaseratio, ζ, is selected which will transmit ions corresponding to theselected overtone through the drift tube. In a 2-phase system, the phaseratio that will transmit ions corresponding to the selected overtonethrough the drift tube is given by the relationship m_(eq)=(ζ+1)/2.Following step 754, the pulse durations of each of the electric fieldactivation sources V₁-V_(M) used in the ion mobility spectrometerinstrument are computed at step 756. The pulse durations for each of theelectric field activation sources V₁-V_(M) can be determined usingwell-known equations based on the frequency or frequency range, FR,determined at step 752 and on the phase ratio, ζ, selected at step 754.Thereafter at step 758, the shape of the pulse width is selected, andthereafter at step 760 the peak voltage of the electric field activationsources V₁-V_(M) is selected. The process 750 advances from step 760 tostep 762, and simultaneously with step 760 the ion source voltagesupply, V_(IS), is controlled at step 764 in a manner that causes theion source, e.g., the ion source 12, to produce ions. The ions producedat step 764 may be produced continuously or may instead be produceddiscretely as described hereinabove. In any case, the control circuit 18is subsequently operable at step 762 to control the electric fieldactivation sources V₁-V_(M), as described hereinabove, to sequentiallyapply electric fields having the selected shapes, durations and peakfield strengths to the various drift tube segments, S₁-S_(N) asdescribed hereinabove by example with reference to FIGS. 2-4D. Steps 760and 762 may be repeated continuously or a finite number of times tothereby operate the ion mobility spectrometer instrument as a continuousor discrete ion mobility filter. It will be understood that steps752-764 are not required to be executed in the illustrated order, andthat one or more of these steps may alternatively be interchanged withone or more other of these steps.

Referring now to FIG. 25, a flowchart of an illustrative process 800 forgenerating a set of overtones for a selected phase ratio, ζ. The process800 illustrated in FIG. 25 may be provided, in whole or in part, in theform of instructions that are stored in the memory unit 20 of thecontrol circuit 18 and that are executable by the control circuit 18 tocontrol an ion mobility spectrometer instrument, e.g., of the typeillustrated and described herein, in accordance with the process 800.The process 800 begins at step 802 where the phase ratio, ζ, isselected. Thereafter at step 804, initial and final frequencies, FI andFF, over which a set of overtones corresponding to the selected phaseratio, ζ, will be generated, and a frequency increment, INC, is alsoselected. Illustratively, the initial frequency, FI, may be selected toproduce an electrical field activation duration that is slightly longerthan necessary to produce the fundamental ion intensity peak for theSOMS system so that the resulting ion intensity vs. frequency spectrumbegins approximately at this fundamental peak. As in the process 750,this initial frequency, FI, is the frequency, f_(eq), at which theequivalent overtone occurs relative to the fundamental frequency, f_(f),of the OMS system, and is given by the relationship f_(eq)=m_(eq)f_(f),where m_(eq) can be determined from the selected phase ratio, ζ,according to the relationship m_(eq)=(ζ+1)/2. Illustratively, the finalfrequency, FF, may be selected to be a frequency beyond which no usefulinformation is expected to occur, or beyond which no ion intensityinformation is sought. In any case, the frequency increment, INC, willtypically be selected to provide desired a frequency resolution.

Following step 804, the pulse durations of each of the electric fieldactivation sources V₁-V_(M) used in the ion mobility spectrometerinstrument are computed at step 806. The pulse durations for each of theelectric field activation sources V₁-V_(M) can be determined usingwell-known equations based on the initial frequency, FI, determined atstep 804 and on the phase ratio, ζ, selected at step 802. Thereafter atstep 808, the shape of the pulse width is selected, and thereafter atstep 810 the peak voltage of the electric field activation sourcesV₁-V_(M) is selected. The process 800 advances from step 810 to step812, and simultaneously with step 810 the ion source voltage supply,V_(IS), is controlled at step 816 in a manner that causes the ionsource, e.g., the ion source 12, to produce ions. The ions produced atstep 816 may be produced continuously or may instead be produceddiscretely as described hereinabove. In any case, the control circuit 18is subsequently operable at step 812 to control the electric fieldactivation sources V₁-V_(M), as described hereinabove, to sequentiallyapply electric fields having the selected shapes, durations and peakfield strengths to the various drift tube segments, S₁-S_(N) asdescribed hereinabove by example with reference to FIGS. 2-4D.Thereafter at step 814, the steps 802-812 are repeated for FI=FI+INCuntil the steps 802-812 are executed for the final frequency, FF. Itwill be understood that steps 802-816 are not required to be executed inthe illustrated order, and that one or more of these steps mayalternatively be interchanged with one or more other of these steps.

Referring now to FIG. 26A, a plot of ion intensity vs. frequency isshown illustrating the result in the frequency domain of a simulatedspectrum resulting from the process 800 of FIG. 25 in which a phaseratio of activation durations of two electric field activation sourcesin a two-phase application is selected to be 3, and the activationdurations of the two electric field activation sources are swept over arange of frequencies. The simulated spectrum illustrated in FIG. 26Aillustratively uses approximately the same fundamental frequency, f_(f),as the simulated spectrum illustrated in FIG. 23A, such that f_(f)≈2kHz. According to the equations m_(eq)=(ζ+1)/2 and f_(eq)=m_(eq)f_(f),the fundamental peak for ζ is the m_(eq)=2 peak that occurs atapproximately f_(eq)=2f_(f)≈4 kHz. Since the illustrated example is of a2-phase system, the SOMS system will have equivalent 3^(rd), 5^(th),7^(th), etc. overtones, and the equivalent 3^(rd) overtone in the ζ=3SOMS system is given by m_(eq)=3((ζ+1)/2)=6 which occurs approximatelyat f_(eq)=6f_(f)≈12 kHz.

It should be noted, as the plot of FIG. 26A illustrates, that the SOMStechnique provides for overtones that are not observed in conventionalOMS systems. In particular, for a 2-phase system, overtones in an OMSsystem include only the odd harmonics, whereas the SOMS resultillustrated in FIG. 26A includes two even harmonics m_(eq)=2, atapproximately 4 kHz and m_(eq)=6 at approximately 12 kHz. Theseharmonics at these frequencies generally are not observed in aconventional OMS system, although SOMS can clearly be used with ζ=3 toobtain an equivalent frequency and packet length to the second and sixthovertones.

It should further be noted that SOMS does not require ζ to be aninteger; only that it be non-negative and non-zero. Referring to FIG.26B, for example, a plot is shown of ion intensity vs. frequencyillustrating the result in the frequency domain of a simulated spectrumresulting from the process 800 of FIG. 25 in which a phase ratio ofactivation durations of two electric field activation sources in atwo-phase application is selected to be the non-integer value 1.25, andthe activation durations of the two electric field activation sourcesare swept over a range of frequencies according to the processillustrated in FIG. 25. The simulated spectrum illustrated in FIG. 26Billustratively uses approximately the same fundamental frequency, f_(f),as the simulated spectrum illustrated in FIG. 23A, such that f_(f)≈2kHz. According to the equations m_(eq)=(ζ+1)/2 and f_(eq)=m_(eq)f_(f),the fundamental peak for ζ=1.25 is the m_(eq)=1.125 peak that occurs atapproximately f_(eq)=1.125f_(f)≈2.5 kHz. Since the illustrated exampleis of a 2-phase system, the SOMS system will have equivalent 3^(rd),5^(th), 7^(th), etc. overtones. The equivalent 3^(rd) overtone in theζ=1.25 SOMS system is given by m_(eq)=3((ζ+1)/2)=3.375 which occursapproximately at f_(eq)=3.375f_(f)≈6.75 kHz, and the equivalent 5^(th)overtone in the ζ=1.25 SOMS system is given by m_(eq)=5((ζ+1)/2)=5.625which occurs approximately at f_(eq)=5.625f_(f)≈11.25 kHz.

The ability to set the phase ratio, ζ, to any positive real numbergreater than zero allows for substantially any equivalent overtonebetween the fundamental overtone for the given ζ and ζ_(max) to begenerated. This results in the ability to collect nearly an unlimitednumber of distinct data points as compared with only a small number ofdefined overtones using OMS.

Referring now to FIG. 27, a flowchart is shown of an illustrativeprocess 850 for investigating overtones at a specified frequency for aselected set of phase ratios, ζ. The process 850 illustrated in FIG. 27may be provided, in whole or in part, in the form of instructions thatare stored in the memory unit 20 of the control circuit 18 and that areexecutable by the control circuit 18 to control an ion mobilityspectrometer instrument, e.g., of the type illustrated and describedherein, in accordance with the process 850. The process 850 begins atstep 852 where a frequency (or small frequency range) of interest isselected. Thereafter at step 854, a set of phase ratios, PR1, PR2, . . ., is selected, over which overtones will be investigated. It should benoted that a selection of the series of phase ratios, PR1, PR2, . . . ,rather than sweeping or scanning ζ from 1 to ζ_(max), avoids duplicationas some overtones will be generated for multiple values of ζ (e.g., the9^(th) overtone can be observed in the data from the 3^(rd) overtone).

In any case, the process 850 advances from step 854 to step 856 wherethe pulse durations of each of the electric field activation sourcesV₁-V_(M) used in the ion mobility spectrometer instrument are computed.The pulse durations for each of the electric field activation sourcesV₁-V_(M) can be determined using well-known equations based on thefrequency, F, determined at step 852 and on the first phase ratio, PR1,in the set of phase ratios determined at step 854. Thereafter at step858, the shape of the pulse width is selected, and thereafter at step860 the peak voltage of the electric field activation sources V₁-V_(M)is selected. The process 850 advances from step 860 to step 862, andsimultaneously with step 860 the ion source voltage supply, V_(IS), iscontrolled at step 866 in a manner that causes the ion source, e.g., theion source 12, to produce ions. The ions produced at step 866 may beproduced continuously or may instead be produced discretely as describedhereinabove. In any case, the control circuit 18 is subsequentlyoperable at step 862 to control the electric field activation sourcesV₁-V_(M), as described hereinabove, to sequentially apply electricfields having the selected shapes, durations and peak field strengths tothe various drift tube segments, S₁-S_(N) as described hereinabove byexample with reference to FIGS. 2-4D. Thereafter at step 864, the steps852-866 are repeated for the next phase ratio in the set of selectedphase ratios until the steps 852-866 are executed for the last phaseratio in the set. It will be understood that steps 852-866 are notrequired to be executed in the illustrated order, and that one or moreof these steps may alternatively be interchanged with one or more otherof these steps.

Referring now to FIG. 28, a flowchart is shown of an illustrativeprocess 900 for investigating overtones in a range of frequencies for aselected set of phase ratios, ζ. The process 900 illustrated in FIG. 28may be provided, in whole or in part, in the form of instructions thatare stored in the memory unit 20 of the control circuit 18 and that areexecutable by the control circuit 18 to control an ion mobilityspectrometer instrument, e.g., of the type illustrated and describedherein, in accordance with the process 900. The process 900 begins atstep 902 where initial and final frequencies, FI and FF, over which aset of overtones will be generated, and a frequency increment, INC, isalso selected. Illustratively, the initial frequency, FI, may beselected to produce an electrical field activation duration that isslightly longer than necessary to produce the fundamental ion intensitypeak for the SOMS system so that the resulting ion intensity vs.frequency spectrum begins approximately at this fundamental peak. As inthe processes 750 and 800, this initial frequency, FI, is the frequency,f_(eq), at which the equivalent overtone occurs relative to thefundamental frequency, f_(f), of the OMS system, and is given by therelationship f_(eq)=m_(eq)f_(f), where m_(eq) can be determined from theselected phase ratio, ζ, according to the relationship m_(eq)=(ζ+1)/2.Illustratively, the final frequency, FF, may be selected to be afrequency beyond which no useful information is expected to occur, orbeyond which no ion intensity information is sought. In any case, thefrequency increment, INC, will typically be selected to provide desireda frequency resolution.

Following step 902, the process 900 advances to step 904 where a set ofphase ratios, PR1, PR2, . . . , is selected, over which overtones willbe investigated. It should be noted again that a selection of the seriesof phase ratios, PR1, PR2, . . . , rather than sweeping or scanning ζfrom 1 to ζ_(max), avoids duplication as some overtones will begenerated for multiple values of ζ. In any case, the process 900advances from step 904 to step 906 where the pulse durations of each ofthe electric field activation sources V₁-V_(M) used in the ion mobilityspectrometer instrument are computed. The pulse durations for each ofthe electric field activation sources V₁-V_(M) can be determined usingwell-known equations based on the initial frequency, FI, determined atstep 902 and on the first phase ratio, PR1, in the set of phase ratiosdetermined at step 904. Thereafter at step 908, the shape of the pulsewidth is selected, and thereafter at step 910 the peak voltage of theelectric field activation sources V₁-V_(M) is selected. The process 900advances from step 910 to step 912, and simultaneously with step 910 theion source voltage supply, V_(IS), is controlled at step 916 in a mannerthat causes the ion source, e.g., the ion source 12, to produce ions.The ions produced at step 916 may be produced continuously or mayinstead be produced discretely as described hereinabove. In any case,the control circuit 18 is subsequently operable at step 912 to controlthe electric field activation sources V₁-V_(M), as describedhereinabove, to sequentially apply electric fields having the selectedshapes, durations and peak field strengths to the various drift tubesegments, S₁-S_(N) as described hereinabove by example with reference toFIGS. 2-4D. Thereafter at step 914, the steps 902-916 are repeated forFI=FI+INC until the steps 902-916 are executed for the final frequency,FF, and this entire process is then repeated for each phase ratio in theset of selected phase ratios until the steps 902-916 are executed forthe last phase ratio in the set. It will be understood that steps912-916 are not required to be executed in the illustrated order, andthat one or more of these steps may alternatively be interchanged withone or more other of these steps.

The various concepts relating to the SOMS system have been describedwith reference to the simplest case; a 2-phase system. In a 2-phasesystem, only a single phase ratio, ζ, may exist, although it can beshown that, in general, a maximum number of phase ratios, MAX_(ζ), forany multiple-phase system is defined by the relationship Max_(ζ)=φ−1. Inthe simplest case in which any such multiple-phase system defines only asingle phase ratio, ζ, it can be shown that a generalized formula fordetermining an equivalent overtone as a function of phase, φ, and phaseratio, ζ, is given by m_(φζh)=[φh+1][(φ−1)ζ+1]/φ, where h is an integerindex beginning with zero and having a step size of one, which occurs atthe frequency f_(eq)=m_(φζh)f_(f). Two special cases of this formula arenoteworthy. The first is the simplest case for this formula in which ζ=1and h=0, and under these conditions the foregoing formula reduces to theOMS case. The second special case is where h=0 and ζ>1, and under theseconditions the above formula produces the fundamental peak of the SOMSsystem defined by φ and ζ. Those skilled in the art will appreciate thatin multiple-phase systems which define more than one phase ratio, theforegoing formula for determining an equivalent overtone as a functionof phase, φ, and phase ratio, ζ, will be more complicated, and in thisregard the foregoing formula serves as a starting point for determiningsuch equivalent overtone values.

While the invention has been illustrated and described in detail in theforegoing drawings and description, the same is to be considered asillustrative and not restrictive in character, it being understood thatonly illustrative embodiments thereof have been shown and described andthat all changes and modifications that come within the spirit of theinvention are desired to be protected. For example, it will beunderstood that the various techniques and processes illustrated anddescribed herein may alternatively or additionally be implemented usingone or more variants of any of the ion mobility spectrometersillustrated in the attached figures and described hereinabove. As oneexample, any such ion mobility spectrometer may be modified to replaceone or more of the mesh gates, e.g., the 90% transmittance first andlast rings 30 ₁ and 30 ₅ of each drift tube section, S₁, S₂, . . . ,with so-called grid-less gates, e.g., annular rings similar or identicalto the concentric rings 30 ₂-30 ₄ positioned between the ion gates 30 ₁and 30 ₅. Those skilled in the art will recognize other modificationsthat may be made to any of the ion mobility spectrometers illustrated inthe attached figures and described hereinabove, and any suchmodifications are contemplated by this disclosure.

What is claimed is:
 1. A method of separating ions as a function of ionmobility in a drift tube partitioned into a plurality of cascaded drifttube segments beginning with a first drift tube segment and advancingsequentially to a last drift tube segment, each drift tube segmentdefining an ion inlet at one end and an ion outlet at an opposite end,the drift tube further including an ion elimination region between anion outlet of each drift tube segment and an ion inlet of a nextadjacent drift tube segment, the ion elimination regions beginning witha first ion elimination region between the ion outlet of the first drifttube segment and the ion inlet of a second drift tube segment andadvancing sequentially to a last ion elimination region coupled to theion outlet of the last drift tube segment, for any integer M greaterthan 1 the method comprising: repeating the following step multipletimes to cause only ions entering the ion inlet of the first drift tubesegment that have a predefined ion mobility or range of ion mobilitiesto traverse the drift tube, for each integer N beginning with 1 andsequentially advancing to M, establishing for a time duration an Nthelectric repulsive field in the Nth ion elimination region and in everyfollowing Mth ion elimination region while establishing for the timeduration an Nth electric drift field in each remaining ion eliminationregion and in each of the plurality of drift tube segments and whiledeactivating for the time duration all non-Nth electric drift fields andnon-Nth electric repulsive fields in each of the ion elimination regionsand in each of the plurality of drift tube segments.
 2. The method ofclaim 1 wherein the last ion elimination region is coupled between theion outlet of the last drift tube segment and the ion inlet of the firstdrift tube segment such that the drift tube defines therein a closed andcontinuous ion travel path, wherein the drift tube includes an ionentrance drift tube segment coupled to one of the plurality of drifttube segments, an ion exit drift tube segment coupled to another one ofthe plurality of drift tube segments and a plurality of ion gates eachcontrollable to pass ions therethrough or block ions from passingtherethrough, and wherein the method further comprises: controlling oneor more of the plurality of ion gates to introduce ions into the via theion entrance drift tube segment, controlling one or more of theplurality of ion gates to direct ions in the drift tube along thecontinuous ion travel path while blocking ions from exiting the drifttube via the ion exit drift tube segment, after the ions in the drifttube have traveled along the continuous ion travel path a selectednumber of times, controlling one or more of the plurality of ion gatesto direct at least some of the ions in the drift tube through the ionexit drift tube segment and out of the drift tube.
 3. The method ofclaim 1 wherein a fundamental frequency is defined by a ratio of a totalnumber of the plurality of drift tube segments and a total drift timethrough the drift tube of ions having the ion mobility or range of ionmobilities, and wherein the method further comprises repeating multipletimes the step of establishing the electric drift fields and theelectric repulsive fields for each of a plurality of different timedurations to cause ions entering the ion inlet of the first drift tubesegment that have an ion mobility or range of ion mobilities at a numberof different overtone frequencies that are functionally related to thefundamental frequency to traverse the drift tube.
 4. The method of claim3 wherein the last ion elimination region is coupled between the ionoutlet of the last drift tube segment and the ion inlet of the firstdrift tube segment such that the drift tube defines therein a closed andcontinuous ion travel path, wherein the drift tube includes an ionentrance drift tube segment coupled to one of the plurality of drifttube segments, an ion exit drift tube segment coupled to another one ofthe plurality of drift tube segments and a plurality of ion gates eachcontrollable to pass ions therethrough or block ions from passingtherethrough, and wherein the method further comprises: controlling oneor more of the plurality of ion gates to introduce ions into the via theion entrance drift tube segment, controlling one or more of theplurality of ion gates to direct ions in the drift tube along thecontinuous ion travel path while blocking ions from exiting the drifttube via the ion exit drift tube segment, after the ions in the drifttube have traveled along the continuous ion travel path a selectednumber of times, controlling one or more of the plurality of ion gatesto direct at least some of the ions in the drift tube through the ionexit drift tube segment and out of the drift tube.
 5. The method ofclaim 1 wherein the time duration of one set of the M electric repulsiveand electric drift fields is different than the time duration of theremaining sets of the M electric repulsive and electric drift fields,and wherein a ratio of the time duration of the one set of the Melectric repulsive and electric drift fields and the time duration ofthe remaining sets of the M electric repulsive and electric drift fieldsdefines a phase ratio that is greater than zero and not equal to unity.6. The method of claim 5 wherein the last ion elimination region iscoupled between the ion outlet of the last drift tube segment and theion inlet of the first drift tube segment such that the drift tubedefines therein a closed and continuous ion travel path, wherein thedrift tube includes an ion entrance drift tube segment coupled to one ofthe plurality of drift tube segments, an ion exit drift tube segmentcoupled to another one of the plurality of drift tube segments and aplurality of ion gates each controllable to pass ions therethrough orblock ions from passing therethrough, and wherein the method furthercomprises: controlling one or more of the plurality of ion gates tointroduce ions into the via the ion entrance drift tube segment,controlling one or more of the plurality of ion gates to direct ions inthe drift tube along the continuous ion travel path while blocking ionsfrom exiting the drift tube via the ion exit drift tube segment, afterthe ions in the drift tube have traveled along the continuous ion travelpath a selected number of times, controlling one or more of theplurality of ion gates to direct at least some of the ions in the drifttube through the ion exit drift tube segment and out of the drift tube.7. The method of claim 5 wherein a fundamental frequency is defined by aratio of a total number of the plurality of drift tube segments and atotal drift time through the drift tube of ions having the ion mobilityor range of ion mobilities, and wherein the method further comprisesrepeating multiple times the step of establishing the electric driftfields and the electric repulsive fields for each of a plurality ofdifferent time durations to cause ions entering the ion inlet of thefirst drift tube segment that have an ion mobility or range of ionmobilities at a number of different overtone frequencies to traverse thedrift tube, wherein each of the number of different overtone frequenciesis a function of the fundamental frequency, the phase ratio and theinteger M.
 8. The method of claim 7 wherein the last ion eliminationregion is coupled between the ion outlet of the last drift tube segmentand the ion inlet of the first drift tube segment such that the drifttube defines therein a closed and continuous ion travel path, whereinthe drift tube includes an ion entrance drift tube segment coupled toone of the plurality of drift tube segments, an ion exit drift tubesegment coupled to another one of the plurality of drift tube segmentsand a plurality of ion gates each controllable to pass ions therethroughor block ions from passing therethrough, and wherein the method furthercomprises: controlling one or more of the plurality of ion gates tointroduce ions into the via the ion entrance drift tube segment,controlling one or more of the plurality of ion gates to direct ions inthe drift tube along the continuous ion travel path while blocking ionsfrom exiting the drift tube via the ion exit drift tube segment, afterthe ions in the drift tube have traveled along the continuous ion travelpath a selected number of times, controlling one or more of theplurality of ion gates to direct at least some of the ions in the drifttube through the ion exit drift tube segment and out of the drift tube.9. The method of claim 5 wherein a fundamental frequency is defined by aratio of a total number of the plurality of drift tube segments and atotal drift time through the drift tube of ions having the ion mobilityor range of ion mobilities, and wherein the method further comprisesrepeating multiple times the step of establishing the electric driftfields and the electric repulsive fields with a sum of the timedurations of each Nth electric repulsive and drift fields defined as aratio of M and the fundamental frequency to cause ions entering the ioninlet of the first drift tube segment that have an ion mobility or rangeof ion mobilities at an overtone frequency to traverse the drift tube,wherein the overtone frequency is defined by the relationship (phaseratio+1)/2.
 10. The method of claim 9 wherein the last ion eliminationregion is coupled between the ion outlet of the last drift tube segmentand the ion inlet of the first drift tube segment such that the drifttube defines therein a closed and continuous ion travel path, whereinthe drift tube includes an ion entrance drift tube segment coupled toone of the plurality of drift tube segments, an ion exit drift tubesegment coupled to another one of the plurality of drift tube segmentsand a plurality of ion gates each controllable to pass ions therethroughor block ions from passing therethrough, and wherein the method furthercomprises: controlling one or more of the plurality of ion gates tointroduce ions into the via the ion entrance drift tube segment,controlling one or more of the plurality of ion gates to direct ions inthe drift tube along the continuous ion travel path while blocking ionsfrom exiting the drift tube via the ion exit drift tube segment, afterthe ions in the drift tube have traveled along the continuous ion travelpath a selected number of times, controlling one or more of theplurality of ion gates to direct at least some of the ions in the drifttube through the ion exit drift tube segment and out of the drift tube.